Kevin Croft

Dietary quercetin attenuates oxidant-induced endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: A critical role for heme oxygenase-1

Publisher: Elsevier BV

Date: 12-2013

DOI: 10.1016/J.FREERADBIOMED.2013.08.185

Abstract: Several lines of evidence indicate that quercetin, a polyphenol derived in the diet from fruit and vegetables, contributes to cardiovascular health. We aimed to investigate the effects of dietary quercetin on endothelial function and atherosclerosis in mice fed a high-fat diet. Wild-type C57BL/6 (WT) and apolipoprotein E gene knockout (ApoE(-/-)) mice were fed: (i) a high-fat diet (HFD) or (ii) a HFD supplemented with 0.05% w/w quercetin (HFD+Q), for 14 weeks. Compared with animals fed HFD, HFD+Q attenuated atherosclerosis in ApoE(-/-) mice. Treatment with the HFD+Q significantly improved endothelium-dependent relaxation of aortic rings isolated from WT but not ApoE(-/-) mice and attenuated hypochlorous acid-induced endothelial dysfunction in aortic rings of both WT and ApoE(-/-) mice. Mechanistic studies revealed that HFD+Q significantly improved plasma F2-isoprostanes, 24h urinary nitrite, and endothelial nitric oxide synthase activity, and increased heme oxygenase-1 (HO-1) protein expression in the aortas of both WT and ApoE(-/-) mice (P<0.05). HFD+Q also resulted in small changes in plasma cholesterol (P<0.05 in WT) and plasma triacylglycerols (P<0.05 in ApoE (-/-)mice). In a separate experiment, quercetin did not protect against hypochlorite-induced endothelial dysfunction in arteries obtained from heterozygous HO-1 gene knockout mice with low expression of HO-1 protein. Quercetin protects mice fed a HFD against oxidant-induced endothelial dysfunction and ApoE(-/-) mice against atherosclerosis. These effects are associated with improvements in nitric oxide bioavailability and are critically related to arterial induction of HO-1.

An overview and update on the epidemiology of flavonoid intake and cardiovascular disease risk

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/D0FO01118E

Abstract: Higher intakes of flavonoid-rich foods are associated with a lower risk of cardiovascular disease in prospective cohort studies.

A single nucleotide polymorphism in the CYP4F2 but not CYP4A11 gene is associated with increased 20-HETE excretion and blood pressure

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2008

DOI: 10.1161/HYPERTENSIONAHA.107.104463

Abstract: Arachidonic acid is a major fatty acid that can be metabolized by the cytochrome P450 enzyme to a number of bioactive eicosanoids. A major metabolite of this oxidation is 20-hydroxyeicosatetraenoic acid, which acts as a potent vasoconstrictor. However, in the kidney, its vasoconstrictor actions can be offset by its natriuretic properties. A guanine-to-adenine polymorphism in the CYP4F2 gene was associated with a reduction in 20-hydroxyeicosatetraenoic acid production in vitro. A thymidine-to-cytosine polymorphism in the CYP4A11 gene reduced catalytic activity by % in vitro and was associated with hypertension. The aim was to determine whether these 2 mutations are associated with urinary 20-hydroxyeicosatetraenoic acid excretion and blood pressure in humans. For the CYP4F2 , 51% were homozygous for the G allele, 40% were carriers, and 9% were homozygous for the A allele. For CYP4A11 , 72% were homozygous for the T allele, 25% were carriers, and 3% were homozygous for the C allele. The CYP4F2 GA/AA genotype was significantly associated with an increase in both 20-hydroxyeicosatetraenoic acid excretion and systolic blood pressure. The CYP4A11 CC/TC genotype was significantly associated with a reduction in 20-hydroxyeicosatetraenoic acid excretion but was not associated with blood pressure. We have demonstrated for the first time in humans that polymorphisms of the CYP4F2 and CYP4A11 genes have opposite effects on 20-hydroxyeicosatetraenoic acid excretion. The positive association between the CYP4F2 GA/AA genotype and both systolic blood pressure and 20-hydroxyeicosatetraenoic acid excretion strengthens a role for 20-hydroxyeicosatetraenoic acid in the modulation of blood pressure.

Urinary 20-hydroxyeicosatetraenoic acid excretion is associated with oxidative stress in hypertensive subjects

Publisher: Elsevier BV

Date: 04-2005

DOI: 10.1016/J.FREERADBIOMED.2004.12.024

Abstract: Oxidative stress has been implicated in the pathogenesis of hypertension. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 product of arachidonic acid metabolism, thought to be involved in the regulation of blood pressure (BP). The metabolism of arachidonic acid by cytochrome P450 enzymes may be a significant source of oxidative stress. F2-isoprostanes are reliable markers of in vivo oxidative damage. gamma-Glutamyl transpeptidase (gamma-GT) has traditionally been associated with alcohol intake or liver dysfunction and may be an early marker of oxidative stress. The objective of the present study was to investigate relationships between 20-HETE excretion and markers of oxidative stress (F2-isoprostanes and gamma-GT). Sixty-nine treated hypertensive subjects underwent measurement of 24-h ambulatory BP, serum gamma-GT, and urinary F2-isoprostane and 20-HETE excretion. 20-HETE excretion was positively associated with 24-h diastolic BP (p = 0.005), alcohol intake (p = 0.008), gamma-GT (p = 0.007), and F2-isoprostanes (p = 0.005). F2-isoprostanes were positively associated with alcohol intake (p = 0.018) and gamma-GT (p = 0.01). In a multivariate regression, gamma-GT remained an independent predictor of 20-HETE excretion, after adjustment for age, gender, BMI, and alcohol intake. In conclusion, the study highlights the positive association observed between 20-HETE excretion and markers of oxidative damage. The study also provides evidence that gamma-GT may be a useful marker of oxidative stress.

Cellular Fatty Acid Profile Distinguishes Burkholderia pseudomallei from Avirulent Burkholderia thailandensis

Publisher: American Society for Microbiology

Date: 10-2003

DOI: 10.1128/JCM.41.10.4812-4814.2003

Abstract: Burkholderia pseudomallei , the cause of melioidosis, can be distinguished from the closely related but nonpathogenic Burkholderia thailandensis by gas chromatography (GC) analysis of fatty acid derivatives. A 2-hydroxymyristic acid derivative (14:0 2OH) was present in 95% of B. pseudomallei isolates and no B. thailandensis isolates. GC mass spectrophotometry confirmed that 2-hydroxymyristic acid was present in B. pseudomallei . GC-fatty acid methyl ester analysis may be useful in distinguishing these two closely related species.

Identifying the metabolomic fingerprint of high and low flavonoid consumers

Publisher: Cambridge University Press (CUP)

Date: 2017

DOI: 10.1017/JNS.2017.27

Abstract: High flavonoid consumption can improve vascular health. Exploring flavonoid–metabolome relationships in population-based settings is challenging, as: (i) there are numerous confounders of the flavonoid–metabolome relationship and (ii) the set of dependent metabolite variables are inter-related, highly variable and multidimensional. The Metabolite Fingerprint Score has been developed as a means of approaching such data. This study aims to compare its performance with that of more traditional methods, in identifying the metabolomic fingerprint of high and low flavonoid consumers. This study did not aim to identify biomarkers of intake, but rather to explore how systemic metabolism differs in high and low flavonoid consumers. Using liquid chromatography–tandem MS, 174 circulating plasma metabolites were profiled in 584 men and women who had complete flavonoid intake assessment. Participants were randomised to one of two datasets: (a) training dataset, to determine the models for the discrimination variables ( n 399) and (b) validation dataset, to test the capacity of the variables to differentiate higher from lower total flavonoid consumers ( n 185). The stepwise and full canonical variables did not discriminate in the validation dataset. The Metabolite Fingerprint Score successfully identified a unique pattern of metabolites that discriminated high from low flavonoid consumers in the validation dataset in a multivariate-adjusted setting, and provides insight into the relationship of flavonoids with systemic lipid metabolism. Given increasing use of metabolomics data in dietary association studies, and the difficulty in validating findings using untargeted metabolomics, this paper is of timely importance to the field of nutrition. However, further validation studies are required.

Relationships of vascular function with measures of ambulatory blood pressure variation

Publisher: Elsevier BV

Date: 03-2014

DOI: 10.1016/J.ATHEROSCLEROSIS.2013.12.026

Abstract: Characteristics of short-term blood pressure (BP) variation may influence cardiovascular disease risk via effects on vascular function. In a cross-sectional study of a group of treated hypertensive and untreated largely normotensive subjects we investigated the relationships of measures of short-term BP variation with brachial artery vasodilator function. A total of 163 treated hypertensive (n = 91) and untreated largely normotensive (n = 72) men and women were recruited from the general population. Measures of systolic and diastolic BP variation were calculated from 24 h ambulatory BP assessments and included: (i) rate of measurement-to-measurement BP variation (SBP-var and DBP-var) and (ii) day-to-night BP dip (SBP-dip and DBP dip). Endothelium-dependent vasodilation was assessed as flow-mediated dilation (FMD) and endothelium-independent vasodilation was assessed in response to glyceryl trinitrate (GTN). Relationships were explored using univariate and multivariate linear regression. The relationships of brachial artery vasodilator function with BP variation were not significantly different between treated hypertensive and untreated subjects, therefore these groups were combined for analysis. In univariate analysis, higher SBP-var (P < 0.001) and lower DBP-dip (P = 0.004) were associated with lower FMD and higher SBP-var (P = 0.002) and lower SBP-dip (P = 0.003) and DBP-dip (P = 0.001) were associated with lower GTN-mediated dilation. In multivariate analysis, lower SBP-dip (P = 0.007) and DBP-dip (P = 0.03) were independently associated with lower GTN response. Our results indicate that a lower day-to-night BP dip is independently associated with impaired smooth muscle cell function. Although rate of BP variation was associated with measures of endothelial and smooth muscle cell function, relationships were attenuated after accounting for age and BP.

Short-term effects of polyphenol-rich black tea on blood pressure in men and women

Publisher: Royal Society of Chemistry (RSC)

Date: 2013

DOI: 10.1039/C2FO30186E

Abstract: There is increasing evidence that black tea polyphenols contribute to vascular health. We have recently shown that regular ingestion of polyphenol-rich black tea over 6 months results in lower systolic and diastolic blood pressure. However, the time course of these effects remains unclear. Therefore, our objective was to determine if short-term effects of tea on blood pressure could contribute to longer-term benefits of regular tea consumption on blood pressure. Men and women (n = 111) were recruited to a randomised placebo-controlled double-blind parallel designed trial. During a 4-week run-in, all participants consumed 3 cups per day of black tea. Participants then consumed 3 cups over 1 day of either powdered black tea solids containing 429 mg of polyphenols (tea), or a control product matched in flavour and caffeine content but containing no tea solids. The 24 h ambulatory blood pressure and heart rate was measured at the end of the 4-week run-in (baseline) and again during the 24 h intervention period. The 24 h day-time and night-time blood pressures were not significantly different between tea and control (P > 0.05). Baseline-adjusted net effects on mean 24 h ambulatory blood pressure for systolic and diastolic blood pressure were -0.2 mm Hg (95% CI, -1.5 to 1.0), P = 0.72, and 0.0 mm Hg (95% CI, -1.0 to 0.9), P = 0.95, respectively. Heart rate was significantly lower for tea compared to control during the night-time and early-morning periods (-2.0 (95% CI, -3.2, -0.8) bpm, and -1.9 (95% CI, -3.7, -0.2) bpm, respectively P < 0.05 for both), but not during the day-time. These results suggest that the longer-term benefits of black tea on blood pressure are unlikely to be due to short-term changes.

Assessment of Tocopherol Metabolism and Oxidative Stress in Familial Hypobetalipoproteinemia

Publisher: Oxford University Press (OUP)

Date: 07-2006

DOI: 10.1373/CLINCHEM.2006.068692

Abstract: Background: Vitamin E supplementation has been recommended for persons with familial hypobetalipoproteinemia (FHBL), a rare disorder of lipoprotein metabolism that leads to low serum α-tocopherol and decreased LDL-cholesterol and apolipoprotein (apo) B. We examined the effect of truncated apoB variants on vitamin E metabolism and oxidative stress in persons with FHBL. Methods: We studied 9 in iduals with heterozygous FHBL [mean (SE) age, 40 (5) years body mass index (BMI), 27 (10) kg/m2] and 7 normolipidemic controls [age, 41 (5) years BMI, 25 (2) kg/m2]. We also studied 3 children—2 with homozygous FHBL (apoB-30.9) and 1 with abetalipoproteinemia—who were receiving α-tocopherol supplementation. We used HPLC with electrochemical detection to measure α- and γ-tocopherol in serum, erythrocytes, and platelets, and gas chromatography–mass spectrometry to measure F2-isoprostanes and tocopherol metabolites in urine as markers of oxidative stress and tocopherol intake, respectively. Results: Compared with controls, persons with FHBL had significantly lower fasting plasma concentrations of total cholesterol [2.4 (0.2) vs 4.7 (0.2) mmol/L], triglycerides [0.5 (0.1) vs 0.9 (0.1) mmol/L], LDL-cholesterol [0.7 (0.1) vs 2.8 (0.3) mmol/L], apoB [0.23 (0.02) vs 0.84 (0.08) g/L], α-tocopherol [13.6 (1.0) vs 28.7 (1.4) μmol/L], and γ-tocopherol [1.0 (0.1) vs 1.8 (0.3) μmol/L] (all P & .03). Erythrocyte α-tocopherol was decreased [5.0 (0.2) vs 6.0 (0.3) μmol/L P & .005], but we observed no differences in lipid-adjusted serum tocopherols, erythrocyte γ-tocopherol, platelet α- or γ-tocopherol, urinary F2-isoprostanes, or tocopherol metabolites. Conclusion: Taken together, our findings do not support the recommendation that persons with heterozygous FHBL receive vitamin E supplementation.

Arachidonic Acid Metabolism In Glucocorticoid-Induced Hypertension

Publisher: Wiley

Date: 07-12-2008

DOI: 10.1111/J.1440-1681.2007.04839.X

Abstract: 1. Products of metabolism of arachidonic acid, such as 20-hydroxyeicosatetraenoic acid (20-HETE), thromboxane A(2) (TXA(2)) and prostaglandin I(2) (PGI(2)), regulate vascular tone. Among them, 20-HETE is a potent constrictor in small arteries that also has natriuretic properties. The present study investigated changes in urinary concentrations of 20-HETE and metabolites of TXA(2) and PGI(2) in glucocorticoid-hypertension in rats, a sodium-independent model. 2. Male Sprague-Dawley rats were treated with saline, adrenocorticotrophic hormone (ACTH 0.2 mg/kg) or dexamethasone (20 microg/kg) by daily s.c. injection for 12 days. Systolic blood pressure (SBP) was measured using the tail-cuff method. Metabolic cages were used for 24 h urine collection. Thymus weight and urinary concentrations of 20-HETE, TXA(2) and PGI(2) were determined. 3. In the present study, SBP was increased by both ACTH (from 102 +/- 2 to 134 +/- 7 mmHg n = 10 P < 0.01) and dexamethasone (from 106 +/- 5 to 122 +/- 4 mmHg n = 10 P < 0.01). Thymus weight, a marker for glucocorticoid activity, was significantly decreased by both ACTH and dexamethasone (56 +/- 9 and 76 +/- 5 mg/100 g bodyweight, respectively n = 10 P' < 0.01) compared with the saline control (151 +/- 5 mg/100 g bodyweight n = 20). Urinary 20-HETE excretion was increased by ACTH (501 +/- 115 pmol/g creatinine n = 10 P' < 0.05) but not by dexamethasone (126 +/- 13 pmol/g creatinine n = 10) compared with the saline control (219 +/- 54 pmol/g creatinine n = 20). Neither ACTH nor dexamethasone affected urinary excretion of TXB(2) or PGI(2) compared with the saline control. 4. In conclusion, ACTH but not dexamethasone increased urinary 20-HETE excretion in male Sprague-Dawley rats. Urinary concentrations of the metabolites TXB(2) and PGI(2) were unchanged in both models of glucocorticoid-hypertension. The vasoconstrictor 20-HETE may play a role in the genesis of ACTH-induced hypertension.

Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity

Publisher: Elsevier BV

Date: 03-2008

DOI: 10.1016/J.BCP.2007.11.002

Abstract: Dietary flavonoids are thought to have health benefits possibly due to antioxidant and anti-inflammatory properties. Many previous in vitro studies examining the bioactivity of flavonoids have failed to consider the effects of metabolic transformation on flavonoid activity. In this study we examined the effect of quercetin and its major metabolites on the production of pro-inflammatory eicosanoids by human leukocytes. Studies comparing free radical scavenging, antioxidant activity and eicosanoid production demonstrate that there are different structural requirements for antioxidant and anti-inflammatory activity. We also investigated the effect of metabolic transformation on flavonoid bioactivity by comparing the activity of quercetin and its major metabolites to inhibit inflammatory eicosanoid production from human leukocytes. Quercetin was a potent inhibitor of leukotriene B4 formation in leukocytes (IC50 approximately 2 microM), and its activity was dependent on specific structural features, particularly the 2,3-double bond of the C-ring. Functionalisation of the 3'-OH group with either methyl or sulfate reduced inhibitory activity up to 50% while a glucuronide substituent at the 3-OH effectively removed the LTB4 inhibitory activity. The major quercetin metabolite quercetin-3'-O-sulfate retained considerable lipoxygenase inhibitory activity (IC50 approximately 7 microM) while quercetin-3-O-glucuronide maintained antioxidant activity but had no lipoxygenase inhibitory activity at physiological concentrations. In conclusion, we have found that structural modification of quercetin due to metabolic transformation had a profound effect on bioactivity, and that the structural features required for antioxidant activity of quercetin and related flavonoids were unrelated to those required for inhibition of inflammatory eicosanoids.

Effects of a nitrate-rich meal on arterial stiffness and blood pressure in healthy volunteers

Publisher: Elsevier BV

Date: 11-2013

DOI: 10.1016/J.NIOX.2013.10.001

Abstract: An increase in nitrate intake can augment circulating nitrite and nitric oxide. This may lead to lower blood pressure and improved vascular function. Green leafy vegetables, such as spinach, are rich sources of nitrate. We aimed to assess the acute effects of a nitrate-rich meal containing spinach on arterial stiffness and blood pressure in healthy men and women. Twenty-six participants aged 38-69years were recruited to a randomized controlled cross-over trial. The acute effects of two energy-matched (2000kJ) meals, administered in random order, were compared. The meals were either high nitrate (220mg of nitrate derived from spinach [spinach]) or low nitrate [control]. Outcome measurements were performed pre-meal and at specific time points up to 210min post meal. Spinach resulted in an eightfold increase in salivary nitrite and a sevenfold increase in salivary nitrate concentrations from pre-meal (P<0.001) to 120min post meal. Spinach compared with control resulted in higher large artery elasticity index (P<0.001), and lower pulse pressure (P<0.001) and systolic blood pressure (P<0.001). Post meal carotid-femoral pulse wave velocity (P=0.07), augmentation index (P=0.63), small artery elasticity index (P=0.98) and diastolic blood pressure (P=0.13) were not significantly altered by spinach relative to control. Therefore, consumption of a nitrate-rich meal can lower systolic blood pressure and pulse pressure and increase large artery compliance acutely in healthy men and women. If sustained, these effects could contribute to better cardiovascular health.

The effects of polyphenols and other bioactives on human health

Publisher: Royal Society of Chemistry (RSC)

Date: 2019

DOI: 10.1039/C8FO01997E

Abstract: Consuming polyphenols is associated with benefits to cardiometabolic health and brain function, which are driven by their complex interrelationship with the gut microbiome, their bioactive metabolites, and other phytochemicals.

The acute effect of flavonoid-rich apples and nitrate-rich spinach on cognitive performance and mood in healthy men and women

Publisher: Royal Society of Chemistry (RSC)

Date: 2014

DOI: 10.1039/C3FO60590F

Abstract: Flavonoid-rich apples and nitrate-rich spinach augment NO status acutely with no concomitant improvements or deterioration in cognitive function and mood.

Phenolic acids protect low density lipoproteins from peroxynitrite-mediated modification in vitro

Publisher: Informa UK Limited

Date: 04-2000

DOI: 10.1179/135100000101535429

Abstract: The role of reactive nitrogen species, such as peroxynitrite, in atherogenesis and the protective effect of dietary phenolic compounds are not yet understood. In this study, we sought firstly to determine whether phenolic acids become nitrated by peroxynitrite and then whether phenolic acid nitration can prevent consumption of gamma-tocopherol and thus enhance the resistance of LDL to oxidation by peroxynitrite. Coumaric acid was found to be readily nitrated by peroxynitrite and it also demonstrated a protective effect on y-tocopherol. Of greater significance was its potent inhibition of lipid peroxidation which was equal to that of caffeic acid.

Induced sputum 8-isoprostane concentrations in inflammatory airway diseases

Publisher: American Thoracic Society

Date: 03-2005

DOI: 10.1164/RCCM.200408-1010OC

Cerebrospinal fluid levels of inflammation, oxidative stress and NAD+are linked to differences in plasma carotenoid concentrations

Publisher: Springer Science and Business Media LLC

Date: 07-2014

DOI: 10.1186/1742-2094-11-117

Antioxidant inhibition of oxygen radicals for measurement of total antioxidant capacity in biological samples

Publisher: Elsevier BV

Date: 06-2006

DOI: 10.1016/J.AB.2006.02.027

Abstract: Few methods for assessing total antioxidant capacity (TAC) include both the percentage of inhibition and the length of inhibition in the measurement. Available methods require above ambient constant temperature incubation, reaction preheating, and/or separate assays for testing hydrophilic and hydrophobic s les. We describe a high-throughput method, antioxidant inhibition of oxygen radicals (AIOR), that overcomes these difficulties. AIOR uses peroxyl radicals to trigger a decrease in fluorescence of the indicator molecule, uroporphyrin I, which is delayed by the presence of antioxidants. The area under the curve is measured by a fluorescence spectrophotometer in a 96-well microplate format, and TAC results are expressed as millimole/liter Trolox equivalents. AIOR is performed at ambient temperature and is applicable to s les in either aqueous or common organic solvents. The reaction between uroporphyrin I and the peroxyl radicals generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) was found to be of first-order kinetics with a mean rate constant (k) of 0.0254. Applications to measure antioxidant capacity are demonstrated on in idual chemicals and biological s les. The method has good linearity, within- and between-assay precision, and recovery.

Higher Habitual Dietary Flavonoid Intake Associates With Less Extensive Abdominal Aortic Calcification in a Cohort of Older Women

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 12-2022

DOI: 10.1161/ATVBAHA.122.318408

Abstract: The extent of abdominal aortic calcification (AAC) is a major predictor of vascular disease events. We have previously found regular apple intake, a major source of dietary flavonoids, associates with lower AAC. Whether total dietary flavonoid intake impacts AAC remains unknown. Here, we extend our observations to habitual intakes of total flavonoids, flavonoid subclasses, and specific flavonoid-containing foods, with the odds of extensive AAC. We conducted cross-sectional analyses on 881 females (median [interquartile range] age, 80 [78–82] years body mass index, 27 [24–30] kg/m 2 ) from the PLSAW (Perth Longitudinal Study of Ageing Women). Flavonoid intake was calculated from food-frequency questionnaires. Calcifications of the abdominal aorta were assessed on lateral lumbar spine images and categorized as less extensive or extensive. Logistic regression was used to investigate associations. After adjusting for demographic, lifestyle and dietary confounders, participants with higher (Q4), compared with lower (Q1) intakes, of total flavonoids, flavan-3-ols, and flavonols had 36% (odds ratio [95% CI], 0.64 [0.43–0.95]), 39% (0.61 [0.40–0.93]) and 38% (0.62 [0.42–0.92]) lower odds of extensive AAC, respectively. In food-based analyses, higher black tea intake, the main source of total flavonoids (75.9%), associated with significantly lower odds of extensive AAC (2–6 cups/d had 16%–42% lower odds compared with 0 daily intake). In a subset of nonconsumers of black tea, the association of total flavonoid intake with AAC remained (Q4 versus Q1 odds ratio [95% CI], 0.11 [0.02–0.54]). In older women, greater habitual dietary flavonoid intake associates with less extensive AAC.

Intake of dietary flavonoids and incidence of ischemic heart disease in the Danish Diet, Cancer, and Health cohort

Publisher: Springer Science and Business Media LLC

Date: 25-10-2022

DOI: 10.1038/S41430-022-01226-Y

Abstract: Few studies have investigated the association between dietary flavonoid intake, including all major subclasses, and the long-term risk of ischemic heart disease (IHD). We examined whether dietary flavonoid intake associated with IHD incidence, assessing the possible modifying role of sex and smoking, in participants from the Danish Diet, Cancer, and Health study. In a cohort study design, 54,496 adults (46.8% male), aged 50–64 years, without a history of IHD, were followed for up to 23 years. Habitual dietary flavonoid intake was estimated from food frequency questionnaires using Phenol-Explorer. Incident cases of IHD were identified within Danish nationwide health registries. Restricted cubic splines in Cox proportional hazards models were used to examine associations between flavonoid intake and IHD risk. During follow-up, 5560 IHD events were recorded. No overall association was seen between total flavonoid intake, nor any subclass, and IHD, following adjustment for demographics, lifestyle, and dietary confounders. Stratified by sex and smoking status, higher intakes of specific subclasses associated with lower IHD risk among ever-smokers [Q5 vs. Q1 flavonols HR (95% CI): 0.90 (0.82, 0.99) flavanol oligo+polymers: 0.88 (0.80, 0.97)], but not among never-smokers, nor either sex specifically. While we did not find clear evidence that higher habitual dietary flavonoid intake was associated with lower IHD risk, these results do not exclude the possibility that certain subclasses may have a protective role in prevention of IHD among population sub-groups this was evident among smokers, who are at a higher risk of atherosclerosis.

Short-term effects of nitrate-rich green leafy vegetables on blood pressure and arterial stiffness in individuals with high-normal blood pressure

Publisher: Elsevier BV

Date: 12-2014

DOI: 10.1016/J.FREERADBIOMED.2014.09.021

Abstract: Evidence for a beneficial effect of dietary nitrate, through the nitrate-nitrite-NO pathway, on measures of cardiovascular function in healthy in iduals is accumulating. It is less clear whether increased dietary nitrate intake from green leafy vegetables would have similar beneficial vascular effects in those at increased risk of developing hypertension. Our aim was to assess the effects of short-term regular consumption of increased nitrate from green leafy vegetables on blood pressure and arterial stiffness in in iduals with high-normal blood pressure. Thirty-eight men and women ages 30-70 years with systolic blood pressure 120 to 139 mm Hg were recruited to a randomized controlled crossover trial. The effects of a 7-day high-nitrate diet intervention (increased nitrate intake by at least 300 mg/day from green leafy vegetables) were compared to a 7-day low-nitrate diet intervention. Outcome measures included pre- and postintervention salivary and plasma nitrate and nitrite concentrations ambulatory, home, and office blood pressure augmentation index and carotid-femoral pulse wave velocity. The high-nitrate diet intervention resulted in at least a fourfold increase in salivary and plasma nitrate and nitrite (P<0.001). Ambulatory, home, and office blood pressure and arterial stiffness were not different between the high-nitrate diet and the low-nitrate diet. Increasing dietary nitrate intake in those with high-normal blood pressure and at increased risk of hypertension may not be an effective short-term strategy to lower blood pressure.

Specific Dietary Polyphenols Attenuate Atherosclerosis in Apolipoprotein E-Knockout Mice by Alleviating Inflammation and Endothelial Dysfunction

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 04-2010

DOI: 10.1161/ATVBAHA.109.199687

Abstract: Objective— Animal and clinical studies have suggested that polyphenols in fruits, red wine, and tea may delay the development of atherosclerosis through their antioxidant and anti-inflammatory properties. We investigated whether in idual dietary polyphenols representing different polyphenolic classes, namely quercetin (flavonol), (−)-epicatechin (flavan-3-ol), theaflavin (dimeric catechin), sesamin (lignan), or chlorogenic acid (phenolic acid), reduce atherosclerotic lesion formation in the apolipoprotein E (ApoE) −/− gene–knockout mouse. Methods and Results— Quercetin and theaflavin (64-mg/kg body mass daily) significantly attenuated atherosclerotic lesion size in the aortic sinus and thoracic aorta ( P .05 versus ApoE −/− control mice). Quercetin significantly reduced aortic F 2 -isoprostane, vascular superoxide, vascular leukotriene B 4 , and plasma-sP-selectin concentrations and augmented vascular endothelial NO synthase activity, heme oxygenase-1 protein, and urinary nitrate excretion ( P .05 versus control ApoE −/− mice). Theaflavin showed similar, although less extensive, significant effects. Although (−)-epicatechin significantly reduced F 2 -isoprostane, superoxide, and endothelin-1 production ( P .05 versus control ApoE −/− mice), it had no significant effect on lesion size. Sesamin and chlorogenic acid treatments exerted no significant effects. Quercetin, but not (−)-epicatechin, significantly increased the expression of heme oxygenase-1 protein in lesions versus ApoE −/− controls. Conclusion— Specific dietary polyphenols, in particular quercetin and theaflavin, may attenuate atherosclerosis in ApoE −/− gene–knockout mice by alleviating inflammation, improving NO bioavailability, and inducing heme oxygenase-1. These data suggest that the cardiovascular protection associated with diets rich in fruits, vegetables, and some beverages may in part be the result of flavonoids, such as quercetin.

Effects of a-Tocopherol and Mixed Tocopherol Supplementation on Markers of Oxidative Stress and Inflammation in Type 2 Diabetes

Publisher: Oxford University Press (OUP)

Date: 03-2007

DOI: 10.1373/CLINCHEM.2006.076992

Abstract: Background: Vitamin E isomers may protect against atherosclerosis. The aim of this study was to compare the effects of supplementation with either α-tocopherol (αT) or mixed tocopherols rich in γ-tocopherol (γT) on markers of oxidative stress and inflammation in patients with type 2 diabetes. Methods: In a double-blind, placebo-controlled trial, 55 patients with type 2 diabetes were randomly assigned to receive (500 mg/day) (a) αT, (b) mixed tocopherols, or (c) placebo for 6 weeks. Cellular tocopherols, plasma and urine F2-isoprostanes, erythrocyte antioxidant enzyme activities, plasma inflammatory markers, and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation. Results: Neutrophil αT and γT increased (both P & .001) with mixed tocopherol supplementation, whereas αT (P & .001) increased and γT decreased (P & .005) after αT supplementation. Both αT and mixed tocopherol supplementation resulted in reduced plasma F2-isoprostanes (P & .001 and P = 0.001, respectively) but did not affect 24-h urinary F2-isoprostanes or erythrocyte antioxidant enzyme activities. Neither αT nor mixed tocopherol supplementation affected plasma C-reactive protein, interleukin 6, tumor necrosis factor-α, or monocyte chemoattractant protein-1. Stimulated neutrophil leukotriene B4 production decreased significantly in the mixed tocopherol group (P = 0.02) but not in the αT group (P = 0.15). Conclusions: The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes. In populations with well-controlled type 2 diabetes, supplementation with either αT or mixed tocopherols rich in γT is unlikely to confer further benefits in reducing inflammation.

Associations between habitual flavonoid intake and hospital admissions for atherosclerotic cardiovascular disease: a prospective cohort study

Publisher: Elsevier BV

Date: 11-2019

DOI: 10.1016/S2542-5196(19)30212-8

The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 2007

DOI: 10.1097/01.HJH.0000254373.96111.43

Equivalent lipid oxidation profiles in advanced atherosclerotic lesions of carotid endarterectomy plaques obtained from symptomatic type 2 diabetic and nondiabetic subjects

Publisher: Elsevier BV

Date: 08-2010

DOI: 10.1016/J.FREERADBIOMED.2010.05.006

Abstract: Type 2 diabetes (T2D) increases the risk for cardiovascular disease and is thought to be associated with increased oxidative stress, a contributor to atherogenesis. Surprisingly, however, there is little direct evidence that T2D-associated oxidative stress results in increased lipid oxidation and/or decreased antioxidant capacity in human atherosclerotic lesions. The aim of this study was to measure vascular lipid oxidation and antioxidants in T2D. The arterial content of oxidized lipid and antioxidants in carotid endarterectomy specimens obtained from diabetic and normoglycemic patients was determined using high-performance liquid chromatography (HPLC), stable isotope dilution gas chromatography-mass spectrometry (GC/MS), and gas-liquid chromatography techniques. The concentrations of hydroxyoctadecanoic acid, F(2)-isoprostanes, and 7-ketocholesterol, as well as alpha-tocopherol, ascorbate, and urate were not different in the two patient groups, whether expressed per unit protein or as a ratio per parent compound. Unexpectedly, a significant decrease in the level of arterial lipid hydroperoxide was found in diabetic patients. Our results do not support the notion that advanced atherosclerotic lesions from T2D patients contain more oxidized lipids than corresponding lesions from nondiabetic subjects.

The effects of vitamin K-rich green leafy vegetables on bone metabolism

Publisher: Elsevier BV

Date: 06-2020

DOI: 10.1016/J.BONR.2020.100274

Effects of low-fat or full-fat fermented and non-fermented dairy foods on selected cardiovascular biomarkers in overweight adults

Publisher: Cambridge University Press (CUP)

Date: 12-06-2013

DOI: 10.1017/S0007114513001621

Abstract: The association between consumption of full-fat dairy foods and CVD may depend partly on the nature of products and may not apply to low-fat dairy foods. Increased circulating levels of inflammatory biomarkers after consumption of dairy product-rich meals suggest an association with CVD. In the present study, we tested the effects of low-fat and full-fat dairy diets on biomarkers associated with inflammation, oxidative stress or atherogenesis and on plasma lipid classes. Within full-fat dairy diets, we also compared fermented v . non-fermented products. In a randomised cross-over study, twelve overweight/obese subjects consumed during two 3-week periods two full-fat dairy diets containing either yogurt plus cheese (fermented) or butter, cream and ice cream (non-fermented) or a low-fat milk plus yogurt diet, with the latter being consumed between and at the end of the full-fat dairy dietary periods. The concentrations of six inflammatory and two atherogenic biomarkers known to be raised in CVD were measured as well as those of plasma F 2 -isoprostanes and lipid classes. The concentrations of six of the eight biomarkers tended to be higher on consumption of the low-fat dairy diet than on that of the fermented dairy diet and the concentrations of two plasmalogen lipid classes reported to be associated with increased oxidisability were also higher on consumption of the low-fat dairy diet than on that of the fermented dairy diet ( P 0·001), although plasma F 2 -isoprostane concentrations did not differ on consumption of any of the diets. On the other hand, the concentrations of plasma sphingomyelin and IL-6 were significantly higher on consumption of the non-fermented dairy diet than on that of the low-fat dairy diet ( P 0·02). In conclusion, short-term diets containing low-fat dairy products did not lead to a more favourable biomarker profile associated with CVD risk compared with the full-fat dairy products, suggesting that full-fat fermented dairy products may be the more favourable.

Long-Term Dietary Nitrate Supplementation Does Not Prevent Development of the Metabolic Syndrome in Mice Fed a High-Fat Diet

Publisher: Hindawi Limited

Date: 05-08-2018

DOI: 10.1155/2018/7969750

Abstract: Background . Nitric oxide (NO) is an important vascular signaling molecule that plays a role in vascular homeostasis. A reduction in NO bioavailability is thought to contribute to endothelial dysfunction, an early risk factor for both cardiovascular disease and type 2 diabetes. Dietary nitrate, through the nitrate-nitrite-NO pathway, may provide an alternate source of NO when the endogenous eNOS system is compromised. In addition to a role in the vascular system, NO may also play a role in the metabolic syndrome including obesity and glucose tolerance. Aim . To investigate the effect of long-term dietary nitrate supplementation on development of the metabolic syndrome in mice fed a high-fat diet. Methods . Following 1 week of acclimatisation, male (6–8 weeks) C57BL6 mice were randomly assigned to the following groups (10/group) for 12 weeks: (i) normal chow + NaCl (1 mmol/kg/day), (ii) normal chow + NaNO 3 (1 mmol/kg/day), (iii) high-fat diet + NaCl (1 mmol/kg/day), and (iv) high-fat diet + NaNO 3 (1 mmol/kg/day). Body weight and food consumption were monitored weekly. A subset of mice (5/group) underwent running wheel assessment. At the end of the treatment period, all mice underwent fasting glucose tolerance testing. Caecum contents, serum, and tissues (liver, skeletal muscle, white and brown adipose, and kidney) were collected, frozen, and stored at −80°C until analysis. Results . Consumption of the high-fat diet resulted in significantly greater weight gain that was not affected by dietary nitrate. Mice on the high-fat diet also had impaired glucose tolerance that was not affected by dietary nitrate. There was no difference in adipose tissue expression of thermogenic proteins or energy expenditure as assessed by the running wheel activity. Mice on the high-fat diet and those receiving dietary nitrate had reduced caecum concentrations of both butyrate and propionate. Conclusions . Dietary nitrate does not prevent development of the metabolic syndrome in mice fed a high-fat diet. This may be due, in part due, to reductions in the concentration of important short-chain fatty acids.

Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus

Publisher: Springer Science and Business Media LLC

Date: 03-2002

DOI: 10.1007/S00125-001-0760-Y

Abstract: We assessed whether dietary supplementation with coenzyme Q(10) improves endothelial function of the brachial artery in patients with Type II (non-insulin-dependent) diabetes mellitus and dyslipidaemia. A total of 40 patients with Type II diabetes and dyslipidaemia were randomized to receive 200 mg of coenzyme Q(10) or placebo orally for 12 weeks. Endothelium-dependent and independent function of the brachial artery was measured as flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation, respectively. A computerized system was used to quantitate vessel diameter changes before and after intervention. Arterial function was compared with 18 non-diabetic subjects. Oxidative stress was assessed by measuring plasma F(2)-isoprostane concentrations, and plasma antioxidant status by oxygen radical absorbance capacity. The diabetic patients had impaired flow-mediated dilation [3.8 % (SEM 0.5) vs 6.4 % (SEM 1.0), p = 0.016], but preserved glyceryl-trinitrate-mediated dilation, of the brachial artery compared with non-diabetic subjects. Flow-mediated dilation of the brachial artery increased by 1.6 % (SEM 0.3) with coenzyme Q(10) and decreased by -0.4 % (SEM 0.5) with placebo (p = 0.005) there were no group differences in the changes in pre-stimulatory arterial diameter, post-ischaemic hyperaemia or glyceryl-trinitrate-mediated dilation response. Coenzyme Q(10) treatment resulted in a threefold increase in plasma coenzyme Q(10) (p < 0.001) but did not alter plasma F(2)-isoprostanes, oxygen radical absorbance capacity, lipid concentrations, glycaemic control or blood pressure. Coenzyme Q(10) supplementation improves endothelial function of conduit arteries of the peripheral circulation in dyslipidaemic patients with Type II diabetes. The mechanism could involve increased endothelial release and/or activity of nitric oxide due to improvement in vascular oxidative stress, an effect that might not be reflected by changes in plasma F(2)-isoprostane concentrations.

Fatty acid and amino acid composition in Haruan as a potential role in wound healing

Publisher: Elsevier BV

Date: 09-1994

DOI: 10.1016/0306-3623(94)90101-5

Abstract: 1. Two species of snakehead fish are available in Sabah, i.e. Channa striatus and Channa melanosoma, and are commonly known as haruan. Haruan is consumed by many Malaysians to induce healing after a clinical operations. However, there is no scientific evidence as yet to substantiate the claim, and so it was decided to analyse the biochemical composition in haruan to determine which compounds may have a possible role or potential in wound healing. 2. S les (midline fillet) of both species were extracted separately in hexane for the qualitative analysis of fatty acids by a gas chromatography, Hewlett-Packard 5890A, using a 10 meter superox 11 column (Alltech) at temperature between 190 and 245 degrees C. Peak areas were calculated automatically using Hewlett-Packard 3393A computing integrator. Subsequently, the amino acid composition was analysed using a precolumn derivatization reverse phase HPLC waters PICO-TAG system. 3. Haruan is found to contain unusually high arachidonic acid (AA) but almost no eicosapentaenoic acid (EPA). AA which is a precursor of prostaglandin may initiate blood clotting and be responsible for growth. Haruan also contains all the essential amino acids for wound healing, particularly glycine which is the most important component of human skin collagen. Therefore, haruan contained all the basic biochemical requirements for wound healing.

Comparison of flavonoid intake assessment methods

Publisher: Royal Society of Chemistry (RSC)

Date: 2016

DOI: 10.1039/C4FO00234B

Abstract: Background : Flavonoids are a erse group of polyphenolic compounds found in high concentrations in many plant foods and beverages.

Isolation, characterization, and immunological effects of α-galacto-oligosaccharides from a new source, the herb Lycopus lucidus Turcz.

Publisher: American Chemical Society (ACS)

Date: 29-06-2010

DOI: 10.1021/JF101217F

Abstract: This study was designed to isolate and characterize a mixture of alpha-galacto-oligosaccharides (GOS) from a new source, the roots of Lycopus lucidus Turcz. (RL), a traditional dietary treatment. In this study, the chemical components and immunological function of RL-GOS were investigated. HPLC analysis showed that the purified RL-GOS was a typical raffinose family oligosaccharide (RFO) with a high stachyose content of 51.8% (w/w), followed by 26.5% raffinose and 10.1% verbascose. Further functional evaluation showed that RL-GOS could elicit a significant increase (p < 0.05 vs control) in humoral immunity, as measured by plaque-forming cell (PFC) generation and serum hemolysin level in response to sheep red blood cells (SRBC) at all three tested doses of RL-GOS (0.75, 1.5, and 3.0 g/kg of BW) in mice. In addition, the cellular immune activity of RL-GOS was also demonstrated by enhancing in vivo delayed-type hypersensitivity (DTH) reaction to SRBC and spleenocyte proliferation response to concanavalin A (p < 0.05, compared with control group). Nevertheless, there were no significant differences in weight gain, lymphoid organ indices, and phagocytosis capacity following RL-GOS treatment. This study provides evidence for the discovery of a new GOS source (20% w/w GOS in fresh roots of L. lucidus Turcz.) and its potential application as an immune stimulant in functional foods.

F2-isoprostanes affect macrophage migration and CSF-1 signalling

Publisher: Elsevier BV

Date: 10-2018

DOI: 10.1016/J.FREERADBIOMED.2018.08.007

Abstract: F

Effect of dietary cholesterol oxidation products on the plasma clearance of chylomicrons in the rat

Publisher: Wiley

Date: 05-2002

DOI: 10.1007/S11745-002-0917-Z

Abstract: Oxidized cholesterols in the diet have been shown to exacerbate arterial cholesterol deposition and the development of atherosclerosis in animal models. Dietary oxidized cholesterols are absorbed through the intestine and incorporated into lymph chylomicrons. The aim of this study was to investigate the effect of oxidized cholesterols on the metabolism of nascent chylomicrons in vivo. It was shown that oxidized cholesterols markedly delay the clearance of chylomicrons from plasma compared to rats given TG alone. However, there was no difference in the clearance of chylomicrons containing oxidized cholesterols vs. purified cholesterol, although the presence of oxysterols did appear to exacerbate the removal of these particles from circulation. The impaired clearance of chylomicrons containing oxidized cholesterols was not due to impaired lipolysis and slower conversion to the remnant form. Moreover, the incorporation of oxidized cholesterols did not alter the hepatic or splenic uptake of chylomicrons compared to chylomicrons isolated from rats given purified cholesterol or TG alone. Collectively, the results of this study suggest that the exacerbated delay in clearance of chylomicron remnants enriched with oxysterols may be due to impaired uptake by tissues other than the liver and spleen. Apolipoprotein (apo) analysis showed that oxysterol incorporation reduced the apoE content and altered the apoC phenotype of chylomicrons, which may have an impact on the removal of chylomicron remnants from plasma. In conclusion, dietary oxysterols appear to have the potential to adversely affect chylomicron metabolism. Therefore, further investigations in humans are required to determine whether dietary oxidized cholesterols found in cholesterol-rich processed foods delay the clearance of postprandial remnants, which may contribute to and exacerbate the development of atherosclerosis.

Induction of Heme Oxygenase-1 In Vivo Suppresses NADPH Oxidase-Derived Oxidative Stress

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 10-2007

DOI: 10.1161/HYPERTENSIONAHA.107.092296

Abstract: Our previous studies suggest that heme oxygenase (HO)-1 induction and/or subsequent bilirubin generation in endothelial cells may suppress superoxide generation of from reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase. In this study, we examined the consequence of HO-1 induction in vivo on NADPH oxidase activity. Three doses of hemin (25 mg · kg −1 , IP, every 48 hours), with or without cotreatment with the HO inhibitor tin protoporphyrin-IX (15 mg · kg −1 , IP), were given to apolipoprotein E–deficient mice, which display vascular oxidative stress. Hemin treatment increased HO-1 expression and activity in aorta (undetectable at baseline) and kidney (by 3-fold) and significantly reduced both NADPH oxidase activity (by ≈25% to 50%) and superoxide generation in situ. The increase in HO-1 activity and inhibition of NADPH oxidase activity by hemin were reversed by tin protoporphyrin-IX and were not associated with changes in Nox2 or Nox4 protein levels. Hemin also reduced plasma F 2 -isoprostane levels by 23%. The inhibition of NADPH oxidase activity by hemin in the aorta was mimicked by bilirubin in vitro (0.01 to 1 μmol/L). Bilirubin also concentration-dependently reduced NADPH oxidase–dependent superoxide production stimulated by angiotensin II in rat vascular smooth muscle cells and by phorbol 12-myristate 13-acetate in human neutrophil-like HL-60 cells. HO-1 overexpression by plasmid-mediated gene transfer in rat vascular smooth muscle cells decreased NADPH-stimulated superoxide production. Thus, systemic expression of HO-1 suppresses NADPH oxidase activity by mechanisms at least partly mediated by the bile pigment bilirubin, thereby reducing oxidative stress.

Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes¹

Publisher: Wiley

Date: 26-11-2007

DOI: 10.1111/J.1464-5491.2007.02281.X

Abstract: To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in in iduals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress. Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored. PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0-9.6) microg/ml, vs. complication-free patients [5.3 (4.7-6.0) microg/ml, P < 0.001] and control subjects [5.3 (4.6-6.1) microg/ml, P < 0.001 anova between three groups, P 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = -0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including log(e)C-reactive protein (CRP r = 0.329), and soluble vascular cell adhesion molecule-1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and log(e)CRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r(2) = 0.427). In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.

Cytochrome P450 metabolites of arachidonic acid are elevated in stroke patients compared with healthy controls

Publisher: Portland Press Ltd.

Date: 09-08-2011

DOI: 10.1042/CS20110215

Abstract: CYP450AAM [arachidonic acid metabolites of the CYP450 (cytochrome P450) enzyme system] have a range of biological functions. CYP450AAM are involved in the pathogenesis of hypertension, renal function and vascular function, yet their role in stroke has not been clarified. We aimed at determining the levels of circulating CYP450 metabolites in patients with acute ischaemic stroke (& h) compared with healthy age- and gender-matched controls. This was a retrospective case-controlled study of 44 acute ischaemic stroke patients and 44 matched controls. A subset of acute ischaemic stroke patients was available for follow-up. Acute ischaemic stroke patients had elevated plasma CYP450AAM, including 20-HETE (20-hydroxyeicosatetraenoic acid) (1921±170 compared with 1108±170 pmol/l, P& .001), EETs (epoxyeicosatrienoic acids) (77.88±3.34 compared with 35.35±3.34 nmol/l, P& .0001) and DiHETEs (dihydroxyeicosatetraenoic acids) (92.87±4.61 compared with 68.17±4.61 nmol/l, P& .0001), as well as increased plasma F2-isoprostane levels (3754±538 compared with 1947±538 pmol/l, P& .02), the latter a marker of oxidative stress, compared with controls. In a subset analysis of the stroke patients, plasma 20-HETE, EETs and F2-isoprostanes were attenuated 30 days after the stroke. Baseline 20-HETE levels were also associated with lesion size and functional indices within the stroke patients. The present study highlights the elevation in CYP450AAM and oxidative stress in acute ischaemic stroke patients. Further investigation of the effect this has on long-term clinical outcome or whether this can be modified by treatment is warranted.

Comparison of nitration and oxidation of tyrosine in advanced human carotid plaque proteins

Publisher: Portland Press Ltd.

Date: 15-02-2003

DOI: 10.1042/BJ20020964

Abstract: The importance of reactive nitrogen species in atherosclerosis remains poorly understood, despite the semi-quantitative evidence for the presence of 3-nitrotyrosine provided by immunohistochemical staining studies. At this time, there appear to be no data describing the prevalence of nitration relative to oxidation in atherosclerotic plaque proteins. The present study used 3-nitrotyrosine and dityrosine as markers of nitration and oxidation respectively to examine the relative abundance of each process. Substantial methodological improvements were required to overcome problems associated with sensitivity and artefactual production of 3-nitrotyrosine when quantified by GLC-MS. It was shown that careful selection of hydrolysis vessel, s le reduction and the use of the oxazolinone derivative provided s le stability and exquisite sensitivity. Using these methods, it was observed that the frequency of nitration was 92±15μmol/mol of tyrosine (0.01%). Dityrosine was present at 1.5±0.14mmol/mol of tyrosine (0.30%) using HPLC/fluorescence thus nitration accounted for approx. 3% of the tyrosine modifications measured. Given that other modifications of tyrosine are known to occur in carotid plaque proteins, the contribution of nitration to the total pool of modified tyrosine is very small. However, the possibility of metabolic processes or chemical agents modifying 3-nitrotyrosine to secondary oxidation products remains an alternative explanation for the low levels demonstrated in this study.

Effect of dietary nitrate supplementation on thermoregulatory and cardiovascular responses to submaximal cycling in the heat

Publisher: Springer Science and Business Media LLC

Date: 22-01-2018

DOI: 10.1007/S00421-018-3809-Z

Abstract: This study investigated whether reported improvements in blood flow distribution, and the possible related effects on thermoregulation during exercise following supplementation with beetroot juice (BR), a rich source of dietary nitrate (NO 12 male endurance-trained cyclists (age 27 ± 6 years, VO Salivary NO This investigation shows that the ergogenic effects and health benefits of BR supplementation, such as augmented cutaneous blood flow, reduced MAP, increased muscle oxygenation, and improved aerobic efficiency may be attenuated when exercise is performed in hot conditions.

Screening plant derived dietary phenolic compounds for bioactivity related to cardiovascular disease

Publisher: Elsevier BV

Date: 04-2018

DOI: 10.1016/J.FITOTE.2017.12.002

Abstract: The potential health benefits of phenolic acids found in food and beverages has been suggested from a number of large population studies. However, the mechanism of how these compounds may exert biological effects is less well established. It is also now recognised that many complex polyphenols in the diet are metabolised to simple phenolic acids which can be taken up in the circulation. In this paper a number of selected phenolic compounds have been tested for their bioactivity in two cell culture models. The expression and activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells and the uptake of glucose in muscle cells. Our data indicate that while none of the compounds tested had a significant effect on eNOS expression or activation in endothelial cells, several of the compounds increased glucose uptake in muscle cells. These compounds also enhanced the translocation of the glucose transporter GLUT4 to the plasma membrane, which may explain the observed increase in cellular glucose uptake. These results indicate that simple cell culture models may be useful to help understand the bioactivity of phenolic compounds in relation to cardiovascular protection.

An improved method for the measurement of urinary and plasma F2- isoprostanes using gas chromatography-mass spectrometry

Publisher: Elsevier BV

Date: 03-1999

DOI: 10.1006/ABIO.1998.3037

Abstract: We have developed an improved method for the measurement of F2-isoprostanes using stable isotope dilution capillary gas chromatography/electron capture negative ionization mass spectrometry (GC-ECNI-MS). The F2-isoprostane family consists of a series of chemically stable prostaglandin F2 (PGF2)-like compounds generated during peroxidation of arachidonic acid in phospholipids. There is evidence that measurement of F2-isoprostanes represents a reliable and useful index of lipid peroxidation and oxidant stress in vivo. Furthermore, 8-epi-PGF2alpha, which is one of the more abundant F2-isoprostanes, is biologically active, being a potent mitogen and vasoconstrictor of rat and rabbit lung and kidney, as well as a partial agonist of platelet aggregation. Measurement of F2-isoprostanes in biological s les is complex and has involved methods which utilize multiple chromatographic steps, including separation by thin-layer chromatography, leading to poor s le recovery. We now present an improved method for the measurement of plasma and urinary F2-isoprostanes using a combination of silica and reverse-phase extraction cartridges, high-performance liquid chromatography (HPLC), and GC-ECNI-MS. Different approaches to the derivatization of the F2-isoprostanes prior to GC-ECNI-MS are also addressed. The overall recovery of F2-isoprostanes is improved (approx 70% for urine) and the within and between assay reproducibility is 6.7% (n = 23) and 3.7% (n = 3), respectively. The mean urinary excretion of F2-isoprostanes in eight healthy males was 365 +/- 5 pmol/mmol creatinine and in three smokers 981 +/- 138 pmol/mmol creatinine. The mean total (free + esterified) plasma F2-isoprostane concentration was 952 +/- 38 pmol/liter, with a within and between assay reproducibility of 8% (n = 13) and 5.6% (n = 3), respectively. This improved method for the measurement of F2-isoprostanes represents a significant advance in terms of the rapidity and yield in the purification of biological s les. The inclusion of HPLC separation enables improved analysis of F2-isoprostanes by GC-MS. This methodology will assist in defining the role of F2-isoprostanes as in vivo markers of oxidant stress in clinical and experimental settings.

Characterising nitric oxide-mediated metabolic benefits of low-dose ultraviolet radiation in the mouse: a focus on brown adipose tissue

Publisher: Springer Science and Business Media LLC

Date: 11-11-2019

DOI: 10.1007/S00125-019-05022-5

Abstract: Exposure to sunlight has the potential to suppress metabolic dysfunction and obesity. We previously demonstrated that regular exposure to low-doses of ultraviolet radiation (UVR) reduced weight gain and signs of diabetes in male mice fed a high-fat diet, in part via release of nitric oxide from skin. Here, we explore further mechanistic pathways through which low-dose UVR exerts these beneficial effects. We fed mice with a luciferase-tagged Ucp1 gene (which encodes uncoupling protein-1 [UCP-1]), referred to here as the Ucp1 luciferase transgenic mouse ('Thermomouse') a high-fat diet and examined the effects of repeated exposure to low-dose UVR on weight gain and development of metabolic dysfunction as well as UCP-1-dependent thermogenesis in interscapular brown adipose tissue (iBAT). Repeated exposure to low-dose UVR suppressed the development of glucose intolerance and hepatic lipid accumulation via dermal release of nitric oxide while also reducing circulating IL-6 (compared with mice fed a high-fat diet only). Dietary nitrate supplementation did not mimic the effects of low-dose UVR. A single low dose of UVR increased UCP-1 expression (by more than twofold) in iBAT of mice fed a low-fat diet, 24 h after exposure. However, in mice fed a high-fat diet, there was no effect of UVR on UCP-1 expression in iBAT (compared with mock-treated mice) when measured at regular intervals over 12 weeks. More extensive circadian studies did not identify any substantial shifts in UCP-1 expression in mice exposed to low-dose UVR, although skin temperature at the interscapular site was reduced in UVR-exposed mice. The appearance of cells with a white adipocyte phenotype ('whitening') in iBAT induced by consuming the high-fat diet was suppressed by exposure to low-dose UVR in a nitric oxide-dependent fashion. Significant shifts in the expression of important core gene regulators of BAT function (Dio2, increased more than twofold), fatty acid transport (increased Fatp2 [also known as Slc27a2]), lipolysis (decreased Atgl [also known as Pnpla2]), lipogenesis (decreased Fasn) and inflammation (decreased Tnf), and proportions of macrophages (increased twofold) were observed in iBAT of mice exposed to low-dose UVR. These effects were independent of nitric oxide released from skin. Our results suggest that non-burning (low-dose) UVR suppresses the BAT 'whitening', steatotic and pro-diabetic effects of consuming a high-fat diet through skin release of nitric oxide, with some metabolic and immune pathways in iBAT regulated by UVR independently of nitric oxide.

Gallic Acid Metabolites are Markers of Black Tea Intake in Humans

Publisher: American Chemical Society (ACS)

Date: 27-05-2000

DOI: 10.1021/JF000089S

Abstract: Gallic acid is one of the main phenolic components of black tea. The objective of this study was to identify urinary gallic acid metabolites with potential for use as markers of black tea intake. In an initial study, nine compounds, assessed by using gas chromatography-mass spectrometry, were found to increase in concentration in urine after 3 cups of black tea over 3 h. A subsequent study employed a controlled crossover design in which 10 subjects consumed 5 cups per day of black tea or water for 4 weeks in random order. Twenty-four hour urine s les were collected at the end of each period. Of the 9 candidate compounds identified in the initial study, only 3 were present at higher concentrations in urine of all 10 subjects during tea-drinking in comparison to water-drinking periods. These compounds were identified as 4-O-methylgallic acid, 3-O-methylgallic acid, and 3, 4-O-dimethylgallic acid, all methyl ether derivatives of gallic acid. It is suggested that these compounds have the potential to be used as markers of black tea intake.

Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study

Publisher: Springer Science and Business Media LLC

Date: 21-04-2021

DOI: 10.1007/S10654-021-00747-3

Abstract: Whether the vascular effects of inorganic nitrate, observed in clinical trials, translate to a reduction in cardiovascular disease (CVD) with habitual dietary nitrate intake in prospective studies warrants investigation. We aimed to determine if vegetable nitrate, the major dietary nitrate source, is associated with lower blood pressure (BP) and lower risk of incident CVD. Among 53,150 participants of the Danish Diet, Cancer, and Health Study, without CVD at baseline, vegetable nitrate intake was assessed using a comprehensive vegetable nitrate database. Hazard ratios (HRs) were calculated using restricted cubic splines based on multivariable-adjusted Cox proportional hazards models. During 23 years of follow-up, 14,088 cases of incident CVD were recorded. Participants in the highest vegetable nitrate intake quintile (median, 141 mg/day) had 2.58 mmHg lower baseline systolic BP (95%CI − 3.12, − 2.05) and 1.38 mmHg lower diastolic BP (95%CI − 1.66, − 1.10), compared with participants in the lowest quintile. Vegetable nitrate intake was inversely associated with CVD plateauing at moderate intakes (~ 60 mg/day) this appeared to be mediated by systolic BP (21.9%). Compared to participants in the lowest intake quintile (median, 23 mg/day), a moderate vegetable nitrate intake (median, 59 mg/day) was associated with 15% lower risk of CVD [HR (95% CI) 0.85 (0.82, 0.89)]. Moderate vegetable nitrate intake was associated with 12%, 15%, 17% and 26% lower risk of ischemic heart disease, heart failure, ischemic stroke and peripheral artery disease hospitalizations respectively. Consumption of at least ~ 60 mg/day of vegetable nitrate (~ 1 cup of green leafy vegetables) may mitigate risk of CVD.

Flaxseed oil supplementation increases plasma F1-phytoprostanes in healthy men

Publisher: Elsevier BV

Date: 10-2009

DOI: 10.3945/JN.109.108316

Abstract: Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been reported to reduce lipid peroxidation products formed from arachidonic acid (F(2)-isoprostanes) in healthy humans, as well as in those under oxidative stress. alpha-Linolenic acid (ALA) is a precursor to EPA and DHA however, its conversion in humans is thought to be inefficient. ALA can also undergo free radical oxidation, forming compounds known as F(1)-phytoprostanes, which are found in all plants and are in high concentrations in plant pollens. In this study, we examined the effect of ALA supplementation on plasma and urine F(1)-phytoprostane and F(2)-isoprostane concentrations in men. Thirty-six nonsmoking men, aged 20-65 y, were recruited from the general population and randomly allocated to consume 9 g/d of either flaxseed oil (62% ALA, 5.4 g/d) or olive oil (placebo) for 4 wk in a parallel design. At baseline and after 4 wk of supplementation, blood s les and a 24-h urine s le were collected for measurement of plasma and urinary F(1)-phytoprostanes and F(2)-isoprostanes and plasma fatty acids. Compared with the olive oil group, plasma phospholipid ALA was greater (P < 0.0001), as were F(1)-phytoprostanes in plasma (P = 0.049) and urine (P = 0.06) in the flaxseed oil group after 4 wk supplementation. Flaxseed oil did not affect plasma or urinary F(2)-isoprostanes. The greater plasma F(1)-phytoprostane concentration in the flaxseed oil group most likely resulted from the increased plasma concentration of the ALA substrate and/or the F(1)-phytoprostane content of the flaxseed oil. Future studies are needed to determine the physiological importance of increased plasma and urine F(1)-phytoprostanes and their relevance to heart disease prevention.

The effect of a single nucleotide polymorphism of the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acid excretion after weight loss

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2014

DOI: 10.1097/HJH.0000000000000208

A Randomized Trial of Effects of Alcohol on Cytochrome P450 Eicosanoids, Mediators of Inflammation Resolution, and Blood Pressure in Men

Publisher: Wiley

Date: 29-08-2017

DOI: 10.1111/ACER.13466

Abstract: Cardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress, and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesized by cytochrome P450 (CYP450) enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F Normotensive men (n = 22) were randomly allocated to drink RW (375 ml/d) or the equivalent volume of dealcoholized red wine (DRW) or water for 4 weeks in a 12-week, 3-period crossover trial. BP, heart rate, 20-HETE, F Drinking RW increased BP (p < 0.05), plasma and urinary 20-HETE (p < 0.05), plasma F This study has shown that men consuming moderate-to-high alcohol as RW for 4 weeks had increased BP, 20-HETE, and oxidative stress, as well as specific SPM that resolve inflammation. These paradoxical findings require further studies to determine whether alcohol stimulates different CYP450 enzymes and whether the findings can be replicated in females.

Dyslipidemic diabetic serum increases lipid accumulation and expression of stearoyl-CoA desaturase in human macrophages.

Publisher: Wiley

Date: 15-06-2011

DOI: 10.1007/S11745-011-3578-5

Abstract: Type 2 diabetes and dyslipidemia are risk factors for cardiovascular disease. However, mechanisms by which hypertriglyceridemia influences atherogenesis remain unclear. We examined effects of dyslipidemic diabetic serum on macrophage lipid accumulation as a model of foam cell formation. Normal human macrophages were cultured in media supplemented with 10% serum from non-diabetic normolipidemic or non-diabetic hypercholesterolemic adults versus adults with Type 2 diabetes diabetes and hypertriglyceridemia or diabetes and hypercholesterolemia. Exposure to diabetic sera resulted in increased macrophage fatty acids (2-3 fold higher, both saturated and unsaturated). Macrophage expression of CD36, scavenger receptor A (SR-A) and stearoyl-CoA desaturase (SCD) was increased, most prominently in macrophages exposed to hypertriglyceridemic diabetic serum (twofold increase in CD36 and fourfold increase in SCD, p < 0.05). In these conditions, RNA inhibition of CD36 reduced macrophage free cholesterol (163.9 ± 10.5 vs. 221.9 ± 26.2 mmol free cholesterol/g protein, p = 0.04). RNA inhibition of SCD decreased macrophage fatty acid content, increased ABCA1 level and enhanced cholesterol efflux (18.0 ± 3.9 vs. 8.0 ± 0.8% at 48 h, p = 0.03). Diabetic dyslipidemia may contribute to accelerated atherosclerosis via alterations in macrophage lipid metabolism favoring foam cell formation. Increased expression of CD36 and SR-A would facilitate macrophage lipid uptake, while increased expression of SCD could block compensatory upregulation of ABCA1 and cholesterol efflux. Further studies are needed to clarify whether modulation of macrophage lipid metabolism might reduce progression of diabetic atherosclerosis.

Microparticles mediate hepatic ischemia-reperfusion injury and are the targets of Diannexin (ASP8597)

Publisher: Public Library of Science (PLoS)

Date: 15-09-2014

DOI: 10.1371/JOURNAL.PONE.0104376

Enzymatically modified isoquercitrin promotes energy metabolism through activating AMPKα in male C57BL/6 mice

Publisher: Royal Society of Chemistry (RSC)

Date: 2019

DOI: 10.1039/C9FO01008D

Abstract: Enzymatically modified isoquercitrin (EMIQ), a quercetin glycoside with a greater bioavailability, is a potential food additive for the regulation of energy metabolism through AMPK phosphorylation.

Changes in oxidative damage, inflammation and [NAD(H)] with age in cerebrospinal fluid

Publisher: Public Library of Science (PLoS)

Date: 14-01-2014

DOI: 10.1371/JOURNAL.PONE.0085335

Chronic activation of AMP‐activated protein kinase prevents 20‐hydroxyeicosatetraenoic acid‐induced endothelial dysfunction

Publisher: Wiley

Date: 28-04-2011

DOI: 10.1111/J.1440-1681.2011.05509.X

Mangostin inhibits the oxidative modification of human low density lipoprotein.

Publisher: Informa UK Limited

Date: 1995

DOI: 10.3109/10715769509064030

Abstract: The oxidation of low density lipoprotein (LDL) may play an important role in atherosclerosis. We investigated the possible antioxidant effects of mangostin, isolated from Garcinia mangostana, on metal ion dependent (Cu2+) and independent (aqueous peroxyl radicals) oxidation of human LDL. Mangostin prolonged the lagtime to both metal ion dependent and independent oxidation of LDL in a dose dependent manner over 5 to 50 microM as monitored by the formation of conjugated dienes at 234 nm (P < 0.001). There was no significant effect of mangostin on the rate at which conjugated dienes were formed in the uninhibited phase of oxidation. Levels of thiobarbituric reactive substances (TBARS) generated in LDL were measured 4 and 24 hours after oxidation with 5 microM Cu2+ in the presence or absence of 50 microM or 100 microM mangostin. We observed an inhibition of TBARS formation with 100 microM mangostin at 4 hours (P = 0.027) but not at 24 hours (P = 0.163). Similar results were observed in the presence of 50 microM mangostin. Mangostin, at 100 microM, retarded the relative electrophoretic mobility of LDL at both 4 and 24 hours after Cu2+ induced oxidation. Mangostin (100 microM) significantly inhibited the consumption of alpha-tocopherol in the LDL during Cu2+ initiated oxidation over a 75 minute period (P < 0.001). From these results, we conclude that mangostin is acting as a free radical scavenger to protect the LDL from oxidative damage in this in vitro system.

A significant proportion of F2-isoprostanes in human urine are excreted as glucuronide conjugates

Publisher: Elsevier BV

Date: 08-2010

DOI: 10.1016/J.AB.2010.04.016

Abstract: The measurement of urinary F(2)-isoprostanes is noninvasive and widely used to assess in vivo oxidative stress in humans. Most studies measure urinary F(2)-isoprostanes in the free form however, many eicosanoids are excreted as urine glucuronide conjugates. Using gas chromatography-mass spectrometry, we examined the extent of glucuronide conjugation of F(2)-isoprostanes in urine collected from healthy men (n = 20) and women (n = 15). Incubation of urine with exogenous glucuronidase led to F(2)-isoprostane concentrations that were approximately 40% higher than untreated s les (P < 0.001). We conclude that a significant proportion of F(2)-isoprostanes in urine are conjugated as glucuronides.

Enzymatically modified isoquercitrin improves endothelial function in volunteers at risk of cardiovascular disease

Publisher: Cambridge University Press (CUP)

Date: 24-12-2020

DOI: 10.1017/S0007114519002137

Abstract: A higher intake of food rich in flavonoids such as quercetin can reduce the risk of CVD. Enzymatically modified isoquercitrin (EMIQ ® ) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential CVD moderating effects in animal studies. The present study aimed to determine whether acute ingestion of EMIQ ® improves endothelial function, blood pressure (BP) and cognitive function in human volunteers at risk of CVD. Twenty-five participants (twelve males and thirteen females) with at least one CVD risk factor completed this randomised, controlled, crossover study. In a random order, participants were given EMIQ ® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow-mediated dilatation (FMD) of the brachial artery was measured before and 1·5 h after intervention. BP, arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ ® treatment resulted in a significantly higher FMD response compared with the placebo (1·80 (95 % CI 0·23, 3·37) % P = 0·025). Plasma concentrations of quercetin metabolites were significantly higher ( P 0·001) after EMIQ ® treatment compared with the placebo. No changes in BP, arterial stiffness, cognitive function or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ ® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ ® consumption.

Effect of weight loss on neutrophil resolvins in the metabolic syndrome

Publisher: Elsevier BV

Date: 09-2019

DOI: 10.1016/J.PLEFA.2019.07.001

Abstract: Non-resolving inflammation associates with obesity and insulin resistance, and may be dependent on the balance of inflammatory substances and specialised pro-resolving mediators of inflammation (SPM) that act to halt the inflammatory response. This controlled trial examined the effect of weight loss on neutrophil synthesis of SPM in volunteers with the metabolic syndrome (MetS). Volunteers with MetS (n = 42) were matched for age and gender and randomly assigned to a 12-wk weight loss program followed by 4-wk weight stabilization or a 16-wk weight maintenance program. At baseline and 16 weeks, isolated neutrophils were stimulated with calcium ionophore and the released SPM were measured by LC-MS/MS. At baseline the SPM resolvin (Rv) E1, 18R-RvE3, RvD2 and Maresin-1 (MaR-1) were detected from stimulated neutrophils. The concentration of released RvE1 was at least 6-fold that of other detected SPM. Weight loss of 4.7 ± 0.8 kg, led to a 2-fold increase in RvE1, P = 0.013, relative to the weight maintenance group. The increase in RvE1 after weight loss was related to, but independent of leukotriene B

Increased nitrate intake from beetroot juice does not alter soluble cellular adhesion molecules and circulating inflammatory cytokines in individuals with treated hypertension: a randomised, controlled trial

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/D2FO02403A

Abstract: Increasing dietary nitrate consumption over 7 days is not effective in reducing soluble inflammatory mediators in in iduals with treated hypertension.

P2Y receptor‐induced EDHF vasodilatation is of primary importance for the regulation of perfusion pressure in the peripheral circulation of the rat

Publisher: Wiley

Date: 04-2002

DOI: 10.1046/J.1365-201X.2002.00956.X

Abstract: Extracellular nucleotides have been shown to induce vasodilatation of conductance arteries by release of the endothelium-derived hyperpolarizing factor (EDHF). As small resistance arteries are of greater importance for blood pressure regulation, a whole rat mesenteric arterial bed preparation was used in the present study when evaluating the physiological relevance for EDHF in mediating nucleotide dilatation. Dilatory responses were examined after pre-contraction with noradrenaline in the presence of 10 mM indomethacin. Adenosine-5'-O-thiodiphosphate (ADPbetaS), adenosine triphosphate (ATP) and uridine triphosphate (UTP) induced vasodilatation (pEC50=6.5-7 and E(max)=40-70%), while uridine diphosphate (UDP) was ineffective. Endothelium-derived hyperpolarizing factor was studied in the presence of 0.5 mM Nvarpi-nitro-L-arginine (L-NOARG). ADPbetaS and UTP induced strong and potent EDHF-dilatations, while ATP only had a weak effect (E(max)=25%). After P2X1 receptor desensitization with 10 microM alphabeta-methylene-adenosine triphosphate, the ATP response was significantly increased (E(max)=65%). Putatively, this could be because of simultaneous activation of both endothelial P2Y receptors and P2X1 receptors on smooth muscle cells, which resulted in the release of EDHF and subsequent hyperpolarization, and depolarization, respectively. Nitric oxide (NO) was studied in the presence of 60 mM K+. ADPbetaS, ATP and UTP induced weak NO dilatations, suggesting a minor role for NO as compared with EDHF. In conclusion, extracellular nucleotides stimulate dilatation by activating P2Y(1) and P2Y(2)/P2Y(4) receptors, but not P2Y(6) receptors. The dilatory responses are mediated primarily by EDHF in the peripheral vascular bed.

Inhibition of lipoprotein oxidation by prenylated xanthones derived from mangostin

Publisher: Informa UK Limited

Date: 2000

DOI: 10.1080/10715760000301161

Abstract: Oxidative damage is thought to play a critical role in cardiovascular and other chronic diseases. This has led to considerable interest in the antioxidant activity of dietary compounds. Flavonoids have received the most attention and much is known about the structural requirements for antioxidant activity. However, little is known about the antioxidant activity of other plant derived phenolic compounds such as the xanthones. We have previously shown that the prenylated xanthone, mangostin, can inhibit the oxidation of low density lipoprotein. In order to examine the effects of structure modification on antioxidant activity of this class of compound we have prepared a number of derivatives of mangostin and tested antioxidant activity in an isolated LDL and plasma assay. The results of this study show that structural modification of mangostin can have a profound effect on antioxidant activity. Derivatisation of the C-3 and C-6 hydroxyl groups with either methyl, acetate, propane diol or nitrile substantially reduces antioxidant activity. In contrast, derivatisation of C-3 and C-6 with aminoethyl derivatives enhanced antioxidant activity, which may be related to changes in solubility. Cyclisation of the prenyl chains had little influence on antioxidant activity.

Absorption of dietary cholesterol oxidation products and incorporation into rat lymph chylomicrons

Publisher: Wiley

Date: 08-1997

DOI: 10.1007/S11745-997-0114-0

Abstract: Cholesterol oxidation products (oxysterols) induce macrophage lipid loading and accumulate in early arterial fatty streaks. The origin of lesion oxysterols has not been elucidated. The absorption of oxysterols from the diet and transport to the arterial wall by postprandial lipoprotein remnants may be a significant source. This study aimed to investigate the extent of oxysterol absorption and the effect on chylomicron composition. Cholesterol was heat-treated, causing 30% oxidation the major oxidation products were 7 beta-hydroxycholesterol, 7-keto-cholesterol, 5 alpha,6 alpha-epoxycholesterol, and 5 beta,6 beta-epoxycholesterol. Conscious lymph-cannulated rats were given a bolus gastric infusion of 50 mg oxidized cholesterol or 50 mg purified cholesterol in a vehicle of triglyceride. In the rats given the oxidized cholesterol, 6% of the oxysterol load was absorbed and incorporated into lymph chylomicrons. Rats given pure cholesterol had no increase in oxysterols above baseline levels. The incorporation of oxysterols into lymph chylomicrons differed over time with 7 beta-hydroxycholesterol, having peak absorption at 3 h, followed by 7-ketocholesterol at 4 h and 5 alpha,6 alpha-epoxy-cholesterol at 5 h. The absorption of oxysterols in animals given the oxidized cholesterol gastric infusate was associated with lymph chylomicron compositional changes at 2-4 h. The oxidized cholesterol-treated group had a twofold increase in the cholesterol (890 +/- 84 micrograms vs. 440 +/- 83 microgram at 3 h) and triglyceride content (19.76 +/- 3.4 micrograms vs. 8.49 +/- 3.8 micrograms at 3 h). This led to a doubling of chylomicron size over this postprandial period, with particles having a mean diameter of 294 nm in the oxidized cholesterol-treated animals, compared to 179 nm in the purified cholesterol group. In conclusion, dietary oxysterols appear to influence postprandial lipoprotein particle size and composition. These changes may have effects on the clearance of chylomicrons from plasma, arterial delivery of oxysterols, and possible deposition in arterial lesions.

Alcohol and endothelial function: A brief review

Publisher: Wiley

Date: 06-12-2001

DOI: 10.1046/J.1440-1681.2001.03572.X

Abstract: 1. In spite of the dose-related effects of alcohol consumption to increase blood pressure, regular light to moderate alcohol intake appears to confer protection against both coronary artery disease and ischaemic stroke. In contrast, heavy alcohol consumption increases the risk of coronary artery disease and the risk of both haemorrhagic and ischaemic stroke. 2. Effects of alcohol consumption on endothelial cell function may be relevant to these disparate effects on cardiovascular outcomes. In in vitro animal studies, low doses of alcohol have been demonstrated to increase release of nitric oxide and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelium-dependent relaxation responses. In contrast, chronic administration of alcohol to rats has generally been associated with tolerance to the acute inhibitory effects of alcohol on endothelium-mediated vasodilatation and may even result in augmentation of such responses. 3. The few human studies to date that have examined the effects of alcohol on endothelial function have focused on postischaemic flow-mediated dilation of the brachial artery (FMD). Although blunted FMD responses have been reported in alcoholic subjects, acute administration of alcohol or short-term interventions to reduce alcohol intake have had no effect to either improve or impair FMD. 4. Further studies in humans assessing acute and longer term dose-related effects of alcohol on endothelial function in both conduit and resistance vessels will be necessary if the relevance of the findings from in vitro and in vivo animal studies are to be understood in the context of the complex interrelationships of alcohol with cardiovascular disease.

Effect of alcohol on cytochrome P450 arachidonic acid metabolism and blood pressure in rats and its modulation by red wine polyphenolics

Publisher: Wiley

Date: 14-02-2006

DOI: 10.1111/J.1440-1681.2006.04337.X

Abstract: Alcohol-induced hypertension is well recognized with clear evidence for a direct pressor effect of chronic alcohol consumption provided by a number of intervention studies in humans. In experimental animals, the effect of alcohol on blood pressure is less consistent however, in Sprague-Dawley rats, alcohol feeding consistently induces a hypertensive response. The mechanism of alcohol-induced hypertension is not clearly understood. Ethanol is known to induce certain cytochrome P450 (CYP) enzymes, particularly the 2E1 isoform, which has been shown to metabolise arachidonic acid (AA) to the 19-hydroxy metabolite (19-HETE), which could have pro-hypertensive activity CYP4A, by comparison, is the principal AA omega-hydroxylase in the liver. Polyphenolic compounds, such as flavonoids, have been shown to inhibit some CYPs. 2. In this study, we determined the effect of alcohol administration on blood pressure and CYP-dependent AA metabolism in the rat and its possible modulation by red wine polyphenols. 3. Thirty male Sprague-Dawley rats were randomly allocated to three groups, which received water, low-dose ethanol (5% v/v) or red wine (diluted to contain 5% ethanol) for a period of 9 weeks. Bodyweight and blood pressure were measured weekly and 24h urine collected at baseline and every 2 weeks. Animals were killed at 9 weeks and blood and tissue s les were collected. The blood pressure of rats fed with alcohol increased significantly over the period of the study compared with controls (P<0.001). The blood pressure of animals fed 5% alcohol in the form of red wine was not significantly different from controls over the study period. The urinary excretion of 20-HETE did not differ significantly among the treatment groups over the study period and there was no effect of any treatment on the metabolism of AA by renal microsomes. Red wine, but not administration of the relatively low dose of alcohol alone, increased the expression of CYP2E1 protein in the liver and kidney and CYP4A in the kidney. Both red wine and alcohol decreased CYP4A protein levels in the liver compared with controls. 4. Our results suggest that constituents of red wine, possibly polyphenols, can attenuate the alcohol-induced rise in blood pressure in the Sprague-Dawley rat, although this effect does not appear to be mediated by the inhibition of CYP-derived AA metabolism.

Oxidative stress in human hypertension: Association with antihypertensive treatment, gender, nutrition, and lifestyle

Publisher: Elsevier BV

Date: 15-01-2004

DOI: 10.1016/J.FREERADBIOMED.2003.10.021

Abstract: There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension. Our aim was to measure markers of oxidative stress in hypertensive subjects, and assess the potential confounding influences of antihypertensive therapy, other cardiovascular risk factors, gender, lifestyle, and nutrition. Markers of oxidative stress, including plasma and 24 h urinary F2-isoprostanes, were measured in 70 untreated (men = 43, women = 27) and 85 treated (men = 43, women = 42) hypertensive subjects and 40 normotensive controls (men = 20, women = 20). Overall, F2-isoprostanes were not elevated in hypertensive subjects compared with controls. However, urinary and plasma F2-isoprostanes were significantly lower in treated compared with untreated hypertensive men, but not women. In hypertensive men, the number of antihypertensive drugs taken was inversely associated with both urinary and plasma F2-isoprostanes (p <.05). Self-reported alcohol intake and biomarkers of alcohol consumption (gamma-glutamyl transpeptidase and high-density lipoprotein cholesterol) were positively associated with plasma but not urinary, F2-isoprostanes in men. Several nutrients were independently associated with plasma and urinary F2-isoprostanes in women. The results do not support the hypothesis that treated or untreated hypertensive subjects are under increased oxidative stress compared with normotensive controls.

Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism

Publisher: Springer Science and Business Media LLC

Date: 09-08-2017

DOI: 10.1186/S40168-017-0312-4

Study of plasma factors associated with neutrophil activation and lipid peroxidation in preeclampsia

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 10-2001

DOI: 10.1161/HY1101.092969

Abstract: Neutrophil activation occurs in women with preecl sia and is resolved after delivery. The present study examined whether circulating factors in plasma of women with preecl sia caused neutrophil activation and lipid peroxidation. Twenty-one women with proteinuric preecl sia were matched for age and gestational age with 19 normal pregnant women. Plasma was collected from all subjects before delivery and at 6 weeks postpartum and incubated with autologous white-cell buffy coat collected at the postpartum visit. Neutrophil activation was assessed by level of CD11b and CD18 expression after incubation with autologous antepartum or postpartum plasma. Lipid peroxidation was assessed by measurement of F 2 -isoprostanes in plasma, plasma–white cell incubates, and urine. Neutrophil CD11b and CD18 expression was not differentially altered by incubation with plasma from either women with preecl sia or normal pregnant women and was similar between groups when incubation was performed with plasma collected after delivery. In preecl sia, plasma F 2 -isoprostanes were significantly increased before and after delivery compared with controls. Plasma F 2 -isoprostanes were increased 2-fold after incubation of plasma with buffy coat, but preecl tic women had higher levels compared with those of controls when either pregnant or postpartum plasma was used. In pregnant preecl tics, plasma F 2 -isoprostanes were positively correlated with lymphocyte count. Six weeks after delivery, plasma F 2 -isoprostanes in the preecl tic women were significantly positively associated with lymphocyte count and cholesterol and negatively associated with albumin. In conclusion, the present study does not suggest that a stable circulating factor causes neutrophil activation in preecl sia. However, lipid peroxidation is elevated before and after delivery in women with preecl sia, which suggests that these women may have an underlying predisposition to increased oxidative stress that may be driven by or contribute to a persistent low-grade inflammatory response.

Dietary flavonoids: effects on endothelial function and blood pressure

Publisher: Wiley

Date: 04-10-2006

DOI: 10.1002/JSFA.2675

Platelet and neutrophil function and eicosanoid release in a subject with abetalipoproteinaemia.

Publisher: Elsevier BV

Date: 02-1993

DOI: 10.1016/0049-3848(93)90032-J

Abstract: It has been suggested that plasma low density lipoprotein (LDL) may affect platelet and leukocyte activity and the release of biologically active eicosanoids which may contribute to the pathogenesis of coronary heart disease. To evaluate the possible biological effects of LDL further we have studied platelet aggregation, leukocyte function and eicosanoid release in a young woman with abetalipoproteinaemia (ABL) who totally lacks LDL. The subject showed decreased platelet response to threshold doses of ADP, collagen and arachidonic acid compared to a matched control measured in parallel or to a larger control group of 22 normal subjects. Aggregation was normal to higher doses of the same agonists. Thromboxane formation in clotted whole blood and in PRP stimulated with collagen was lower for the ABL subject than the control group. Neutrophil function assessed by chemiluminescence following stimulation with PMA, zymosan and FMLP was normal for the ABL subject, although the release of leukotriene B4 from calcium ionophore stimulated cells less than controls. Neutrophil platelet activating factor (PAF) formation and half life in plasma was not altered in ABL. The fatty acid composition of plasma, platelet and erythrocyte membrane phospholipids showed particularly low levels of linoleic acid in ABL compared to controls. Platelet phospholipids from the ABL subject also showed low levels of arachidonic acid. The decrease in eicosanoid formation seen in ABL may be the result of altered fatty acid composition of cell membrane phospholipids, or perhaps a defect in arachidonate mobilization. These results indicate that in a subject who lacks circulating LDL the behaviour of platelets and neutrophils in some in vitro tests is altered, although the extent to which these effects are reflected in vivo with regard to inflammatory and thrombotic mechanisms is not known.

An improved mass spectrometry-based measurement of NO metabolites in biological fluids

Publisher: Elsevier BV

Date: 03-2013

DOI: 10.1016/J.FREERADBIOMED.2012.12.002

Abstract: Assessment of NO metabolism in vivo relies on the accurate measurement of its metabolites nitrite (NO(2)(-)), nitrate (NO(3)(-)), and nitrosothiols (RSNOs) in biological fluids. We report a sensitive method to simultaneously determine NO(2)(-) and NO(3)(-) in biological matrixes. Tetraoctylammonium was used to catalyze the complete conversion of NO(2)(-) and NO(3)(-) to stable pentafluorobenzyl (PFB) derivatives directly from aqueous acetone medium before gas chromatography and negative-ion chemical ionization mass spectrometry (GC/NICI/MS). This catalyst dramatically improved the yield of PFB derivatives for NO(2)(-) (4.5 times) and NO(3)(-) (55 times) compared to noncatalyzed derivatization methods. Analysis was performed using (15)N-labeled internal standards by selected-ion monitoring at m/z 46 for fragment NO(2)(-) and m/z 47 for its isotope analogue, (15)NO(2)(-), and m/z 62 for NO(3)(-) and m/z 63 for (15)NO(3)(-). This method allowed specific detection of both PFB derivatives over a wide dynamic range with a limit of detection below 4.5 pg for NO(2)(-) and 2.5 pg for NO(3)(-). After the specific conversion of RSNOs by HgCl(2) to NO(2)(-), this GC/NICI/MS analysis was used to measure RSNOs in plasma. A further comparison with the widely used tri-iodide chemiluminescence (I(3)(-)-CL) assay indicated that the GC/MS assay validated the lower physiological RSNO and nitrite levels reported using I(3)(-)-CL detection compared with values obtained using UV-photolysis methods. Plasma levels of RSNOs determined by GC/MS and I(3)(-)-CL were well correlated (r = 0.8). The improved GC/MS method was successfully used to determine the changes in plasma, urinary, and salivary NO(2)(-) and NO(3)(-) as well as plasma RSNOs in humans after either a low-NO(3)(-) or a high-NO(3)(-) meal.

No effect of 4 wk of nitrate-rich vegetable consumption on blood pressure: reflections for future research Reply

Publisher: Elsevier BV

Date: 12-2018

DOI: 10.1093/AJCN/NQY246

Urinary 20-Hydroxyeicosatetraenoic Acid is Associated with Endothelial Dysfunction in Humans

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 27-07-2004

DOI: 10.1161/01.CIR.0000136808.72912.D9

Abstract: Background— 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 (ω-hydroxylase) metabolite of arachidonic acid with vasoconstrictor activity that may be involved in the pathogenesis of hypertension. In humans, there are few data relating 20-HETE to vascular pathophysiology. This study aimed to determine whether urinary 20-HETE excretion is related to blood pressure or vascular endothelial function in humans. Methods and Results— Sixty-six subjects (37 males, 29 females), including 29 with untreated hypertension, had urinary 20-HETE excretion measured by gas chromatography/mass spectrometry. There was no significant difference for 20-HETE excretion between hypertensive and normotensive subjects. 20-HETE excretion was positively related to body mass index and sodium excretion. There was a significant inverse association between urinary 20-HETE and endothelium-dependent vasodilation measured by flow-mediated dilation of the brachial artery ( P =0.006). There was no association with vasodilator responses to nitroglycerin. In multiple regression analysis, 20-HETE remained an independent predictor of endothelium-dependent vasodilation after adjustment for age, body mass index, and blood pressure. When gender was included in the model, the relationship between 20-HETE and flow-mediated dilation was attenuated. Separate analysis by gender revealed that in women, hypertensive subjects had significantly higher 20-HETE excretion than normotensive subjects, but this was not seen in men. In women, 20-HETE was positively related to diastolic and systolic blood pressure. In men, 20-HETE was positively related to body mass index. Conclusions— This is the first demonstration of an association between 20-HETE excretion and in vivo vascular function in humans. Given the negative modulatory role of nitric oxide on ω-hydroxylase, the present results suggest a potentially important role for 20-HETE in human vascular physiology.

Red wine polyphenols, in the absence of alcohol, reduce lipid peroxidative stress in smoking subjects

Publisher: Elsevier BV

Date: 03-2001

DOI: 10.1016/S0891-5849(00)00497-4

Abstract: Phenolic compounds in red wine can exert antioxidant effects on in vitro lipoprotein oxidation. This has led to speculation that red wine consumption mediates unique anti-atherosclerotic effects compared to other alcoholic beverages. However, studies assessing the effects of red wine consumption on lipoprotein oxidation ex vivo have not been conclusive. The recent identification of the F2-isoprostanes as oxidative products of arachidonic acid has provided a reliable measure of in vivo lipid peroxidation. This randomized trial investigated changes in plasma and urinary F2-isoprostane concentrations following red wine, white wine, or dealcoholized red wine consumption in humans. Eighteen male smokers consumed, in random order, red wine, white wine, or dealcoholized red wine, for two weeks with one week washout between beverages. Plasma and urinary F2-isoprostane concentrations were measured before and after each beverage. Serum gamma-glutamyl transpeptidase (gamma-GT) and urinary 4-O -methylgallic acid were measured as markers of alcohol consumption and phenolic acid absorption, respectively. Plasma F2-isoprostanes (p < .05) decreased significantly with dealcoholized red wine but not with the alcohol-containing beverages. Urinary excretion of F2-isoprostanes showed a similar trend. gamma-GT decreased significantly with dealcoholized red wine and increased with both alcohol-containing beverages (p < .01). Urinary excretion of 4-O-methylgallic acid increased significantly (p < .001) in the 24 h urine s les following red wine or dealcoholized red wine ingestion, but not with white wine. Serum urate increased and beta-carotene decreased with both alcoholic beverages relative to dealcoholized red wine. There was no change in the antioxidants alpha- and gamma-tocopherol or vitamin C with any of the beverages. The results suggest that polyphenols in dealcoholized red wine can reduce in vivo lipid peroxidation as measured by F2-isoprostanes in smoking subjects. However, no reduction in lipid peroxidation was observed following red or white wine consumption, suggesting that any protective effects of wine drinking on cardiovascular disease are unlikely to be related to inhibition of lipid oxidation.

Retinol supplementation in murine Plasmodium berghei malaria: Effects on tissue levels, parasitaemia and lipid peroxidation

Publisher: Elsevier BV

Date: 04-2007

DOI: 10.1016/J.IJPARA.2006.10.011

Abstract: Reduced plasma retinol concentrations occur in human malaria but the benefits of supplementation remain uncertain. We assessed the in vivo efficacy of retinol administration, and its effect on lipid peroxidation, in a Plasmodium berghei murine model. Animals received vehicle (n=17) or retinol (i) before P. berghei inoculation (four doses), (ii) at parasitaemia 10-15% (three to four doses) or (iii) before and after inoculation (six to seven doses n=15 in each group), with euthanasia on day 8 post-inoculation or when the parasitaemia exceeded 50%. Multiple-dose pre-inoculation retinol reduced endpoint parasitaemia by 24% (P=0.001 versus controls). A reduction of 18% (P=0.042) was observed when retinol was given to parasitaemic animals. Retinol was ineffective when given both before and after infection (11% reduction P=0.47). Although retinol supplementation did not change plasma retinol concentrations, liver retinol content increased and correlated inversely with endpoint parasitaemia (r=-0.45, P=0.001). Malaria infection augmented concentrations of the free radical lipid peroxidation end-product F(2)-isoprostanes in plasma, erythrocytes and liver by 1.8-, 2.8- and 4.9-fold, respectively, but retinol supplementation had no effect on these increases. Consistent with some human malaria studies, prophylactic retinol reduces P. berghei parasitaemia. This effect relates to augmentation of tissue retinol stores rather than to retinol-associated changes in oxidant status.

Platelet-activating factor biosynthesis in rat vascular smooth muscle cells

Publisher: S. Karger AG

Date: 1994

DOI: 10.1159/000159040

Abstract: The ability of platelet-activating factor (PAF) receptor antagonists to protect rats from the cardiovascular collapse induced by large doses of endothelin 1 led us to examine the capacity of rat cultured vascular smooth muscle cells to produce PAF and also to evaluate its potential functional roles in this cell type. Adenosine triphosphate and the vasoactive peptides, endothelin 1, angiotensin II, and arginine vasopressin, each elicited an increase in the PAF level in extracts of rat cultured vascular smooth muscle cells as determined by bioassay. PAF was not detectable (above 20 fmol/mg protein) in the supernatants of these cells. The identity of the bioactivity as PAF was confirmed by GC/MS which indicated that more than 80% of the PAF was 1-O-hexadecyl-2-acetyl-3-sn-glyceryl-phosphorylcholine. Exogenous PAF (100 nM) elicited increases in intracellular calcium that were inhibited by WEB 2086 (10 microM). Endothelin 1, at a concentration which stimulated PAF synthesis, (1 nM), elicited increases in intracellular calcium levels that were not inhibited by WEB 2086 (10 microM). Thus, endogenous PAF is unlikely to be involved in the endothelin-1-induced calcium increases. Although WEB 2086 (3-100 microM) inhibited concentration dependently fetal calf serum (10% v/v) induced [3H]-thymidine incorporation, reaching a maximum effect at 30 microM of 40-50% reduction, in parallel experiments WEB 2086 had no effect on serum-induced increases in cell numbers. We conclude that PAF is produced and retained by cultured rat vascular smooth muscle and that it is unlikely to contribute to the signaling of increases in intracellular calcium or proliferation.

20-Hydroxyeicosatetraenoic acid synthesis is increased in human neutrophils and platelets by angiotensin II and endothelin-1

Publisher: American Physiological Society

Date: 04-2011

DOI: 10.1152/AJPHEART.00733.2010

Abstract: The cytochrome P-450 arachidonic acid metabolite 20-HETE is central to the regulation of vascular tone, renal function, and blood pressure and is synthesized in the rat kidney in response to angiotensin II (ANG II) and endothelin-1 (ET-1). There are very few studies examining the cellular synthesis of 20-HETE in humans. We aimed to measure human neutrophil and platelet 20-HETE levels under basal conditions and after ANG II, ET-1, and calcium ionophore (CaI). 20-HETE was measured in human platelets and neutrophils after saline (control), CaI (2.5 μg/ml), and ANG II or ET-1 (10 nmol/l-1 μmol/l) incubations. The effect of cells, which were preincubated with the ω-hydroxylase inhibitor N-hydroxy- N′-(4- butyl-2-methylphenyl) (HET0016, 10 nM), ANG II types 1 or 2 (AT 1 or AT 2 ) receptor inhibition with irbesartan (1 μmol/l) or PD-123319 (1 μmol/l), or endothelin receptor subtypes A or B (ET A or ET B ) receptor inhibition with BQ-123 or BQ-778 (100 nmol/l), was studied. Neutrophil and platelet content and release of 20-HETE was significantly increased by CaI and blocked by the ω-hydroxylase inhibitor HET0016. ANG II and ET-1 significantly increased neutrophil and platelet content and release of 20-HETE. ANG II increased 20-HETE via the AT 2 receptor. ET-1 increased 20-HETE through the ET B receptor in platelets and both the ET A and ET B receptors in neutrophils. These studies show that human platelets and neutrophils synthesize 20-HETE in response to ANG II and ET-1. 20-HETE synthesis in both cell types was predominantly mediated via the AT 2 and ET B receptors. Stimulation via these receptor pathways has generally been thought to be cardioprotective and requires further studies in clinical situations associated with low-grade inflammation or where ANG II and ET-1 are elevated to clarify the role of 20-HETE.

Acute effects of chlorogenic acid on nitric oxide status, endothelial function, and blood pressure in healthy volunteers: A randomized trial

Publisher: American Chemical Society (ACS)

Date: 04-09-2012

DOI: 10.1021/JF303440J

Abstract: There is mounting evidence that specific dietary polyphenols can enhance vascular health by augmenting nitric oxide. Our aim was to investigate the acute effects of chlorogenic acid, an important dietary phenolic acid present in coffee (400 mg, equivalent to 2 cups of coffee), on nitric oxide status, endothelial function, and blood pressure. Healthy men and women (n = 23) were recruited to a randomized, double-blind, placebo-controlled, crossover trial. Chlorogenic acid resulted in significantly higher plasma concentrations of chlorogenic acid (P 0.10) and the measure of endothelial function (P = 0.60) were not significantly influenced. Chlorogenic acid can lower blood pressure acutely, an effect that, if sustained, would benefit cardiovascular health.

The Efficacy of Quercetin in Cardiovascular Health

Publisher: Springer Science and Business Media LLC

Date: 18-08-2015

DOI: 10.1007/S13668-015-0137-3

Hypolipidemic and cardioprotective benefits of a novel fireberry hawthorn fruit extract in the JCR:LA-cp rodent model of dyslipidemia and cardiac dysfunction

Publisher: Royal Society of Chemistry (RSC)

Date: 2016

DOI: 10.1039/C6FO01023G

Abstract: Hawthorn is a widely used herbal alternative medicine for the treatment of various cardiovascular diseases.

Higher plasma levels of F₂-isoprostanes are associated with slower psychomotor speed in healthy older adults

Publisher: Informa UK Limited

Date: 03-04-2019

DOI: 10.1080/10715762.2018.1513133

Abstract: Oxidative stress has been identified as a process which is detrimental to brain health, and associated with age-related cognitive declines. Few studies to-date have examined the relationship between

Fish oil supplementation in pregnancy lowers F2-isoprostanes in neonates at high risk of atopy

Publisher: Informa UK Limited

Date: 03-2004

DOI: 10.1080/10715760310001656722

Abstract: The anti-inflammatory properties of n-3 polyunsaturated fatty acids (n-3 PUFA) have suggested a potential role of these nutrients in dietary modification for prevention of allergic disease in early life. As oxidative stress is known to modify antigen presenting cell (APC) signalling and resulting immune responses, we examined the effects of maternal n-3 PUFA supplementation in pregnancy on markers of oxidative stress and APC function in neonates at high risk of allergy. Eighty-three pregnant atopic women were randomised to receive 4 g daily of either fish oil (n = 40) or olive oil (n = 43) capsules in a controlled trial from 20 weeks gestation until delivery. Plasma (cord blood) and urinary F2-isoprostanes were measured as markers of lipid peroxidation. Cord erythrocyte fatty acids and markers of APC function (HLA-DR expression and cytokine responses) were measured and related to levels of plasma F2-isoprostanes. Maternal fish oil supplementation lowered plasma (p < 0.0001) and urinary (p = 0.06) F2-isoprostanes. HLA-DR expression on APC was not different between the groups. In multiple regression analysis, 28.8% of the variance in plasma F2-isoprostanes was explained by positive relationships with erythrocyte arachidonic acid (AA) and monocyte HLA-DR expression and a negative relationship with erythrocyte eicosapentaenoic acid (EPA). This study shows that maternal supplementation with fish oil can attenuate neonatal lipid peroxidation. Clinical follow-up of these infants will help to determine if there are sustained effects on postnatal oxidative stress and expression of allergic disease.

Chronic nitrite treatment activates adenosine monophosphate-activated protein kinase-endothelial nitric oxide synthase pathway in human aortic endothelial cells

Publisher: Elsevier BV

Date: 05-2021

DOI: 10.1016/J.JFF.2021.104447

Early versus late parenteral nutrition in term and late preterm infants: study protocol for a randomised controlled trial

Publisher: Springer Science and Business Media LLC

Date: 30-08-2022

DOI: 10.1186/S12887-022-03569-8

Abstract: Despite the wide use of parenteral nutrition (PN) in neonatal intensive care units (NICU), there is limited evidence regarding the optimal time to commence PN in term and late preterm infants. The recommendations from the recently published ESPGHAN/ESPEN/ESPR/CPEN and NICE guidelines are substantially different in this area, and surveys have reported variations in clinical practice. The aim of this randomised controlled trial (RCT) is to evaluate the benefits and risks of early versus late PN in term and late preterm infants. This study is a single-centre, non-blinded RCT in the NICU of Perth Children’s Hospital, Western Australia.A total of 60 infants born ≥34 weeks of gestation who have a high likelihood of intolerance to enteral nutrition (EN) for at least 3-5 days will be randomised to early (day 1 or day 2 of admission) or late commencement (day 6 of admission) of PN after informed parental consent. In both groups, EN will be commenced as early as clinically feasible. Primary outcomes are plasma phenylalanine and plasma F 2 -isoprostane levels on Day 4 and Day 8 of admission. Secondary outcomes are total and in idual plasma amino acid profiles, plasma and red blood cell fatty acid profiles, in-hospital all-cause mortality, hospital-acquired infections, length of hospital/NICU stay, z scores and changes in z scores at discharge for weight, height and head circumference, time to full EN, duration of respiratory (mechanical, non-invasive) support, duration of inotropic support, the incidence of hyper and hypoglycaemia, incidence of metabolic acidosis, liver function, blood urea nitrogen, and C-reactive protein (CRP). This RCT will examine the effects of early versus late PN in term and late preterm infants by comparing key biochemical and clinical outcomes and has the potential to identify underlying pathways for beneficial or harmful effects related to the timing of commencement of PN in such infants. ANZCTR ACTRN12620000324910 (3rd March 2020)

Reduced metal ion concentrations in atherosclerotic plaques from subjects with Type 2 diabetes mellitus

Publisher: Elsevier BV

Date: 06-2012

DOI: 10.1016/J.ATHEROSCLEROSIS.2012.03.015

Abstract: Transition metal ions have been implicated in atherosclerosis. The goal of this study was to investigate whether metal ion levels were higher in people with diabetes, in view of their increased risk of aggravated atherosclerosis. Absolute concentrations of iron, copper, zinc and calcium, and products of protein and lipid oxidation were quantified in atherosclerotic lesions from subjects with (T2DM, n=27), without Type 2 diabetes (nonDM, n=22), or hyperglycaemia (HG, n=17). Iron (P<0.05), zinc (P<0.01) and calcium (P=0.01) were lower in T2DM compared to nonDM subjects. Copper levels were comparable. A strong correlation (r=0.618 P<0.001) between EPR-detectable and total iron in nonDM patients was not seen in T2DM. X-ray fluorescence microscopy revealed "hot spots" of iron in both T2DM and nonDM. Calcium and zinc co-localised and levels correlated strongly. F(2)-isoprostanes (P<0.05) and di-Tyr/Tyr ratio (P<0.025), oxidative damage markers were decreased in T2DM compared to nonDM, or HG. Advanced atherosclerotic lesions from T2DM subjects unexpectedly contained lower levels of transition metal ions, and protein and lipid oxidation products, compared to nonDM and HG. These data do not support the hypothesis that elevated metal ion levels may be a major causative factor in the aggravated atherosclerosis observed in T2DM patients.

Dietary nitrate supplementation does not improve cycling time-trial performance in the heat

Publisher: Informa UK Limited

Date: 07-08-2018

DOI: 10.1080/02640414.2017.1364404

Abstract: This investigation examined the effect of beetroot juice (BR) supplementation, a source of dietary nitrate (NO

Effect of ascorbic acid supplementation on plasma isoprostanes in haemodialysis patients [6]

Publisher: Oxford University Press (OUP)

Date: 04-10-2006

DOI: 10.1093/NDT/GFI154

Simultaneous quantitative analysis of polyphenolic compounds in human plasma by liquid chromatography tandem mass spectrometry

Publisher: Wiley

Date: 08-08-2019

DOI: 10.1002/JSSC.201900339

Abstract: A diet rich in polyphenolic compounds has recognized health benefits, and as such is routinely monitored as part of dietary intervention studies. A method for the simultaneous determination of 36 phenolic compounds, including phenolic acids and flavonoids, using liquid chromatography and tandem mass spectrometry is described here. The target analytes were quantified based on their specific mass spectral fragments using a selected reaction monitoring approach. A C18 column with embedded aromatic functionality ensured separation of all phenolic compounds studied which included several pairs of isomers. S le preparation involved the use of β-glucuronidase to release the phenolic compounds from their conjugated forms. The intra-day and inter-day precision and accuracy was less than 7% for all phenolic compounds studied. Recoveries, where plasma was spiked with three different concentrations of the analytes, ranged from 95-115%. The limits of detection and quantification were 0.23-3.89 and 1.15-7.79 nM, respectively. The method was successfully applied to real s les and the range reported for each phenolic compound, with the exception of hydroferulic acid, nordihydroguaiaretic acid, methylgallate, and m-coumaric acid, was at least an order of magnitude higher than the limit of quantification for the method.

Vitamin E metabolism

Publisher: Elsevier BV

Date: 10-2007

DOI: 10.1016/J.MAM.2006.12.007

Abstract: The aim of this paper is to provide an overview of vitamin E metabolism. The topics covered include: major classes of vitamin E metabolites their production pathways and route of excretion possible biological activities of vitamin E metabolites and use of vitamin E metabolites as markers of oxidant generation. Recent investigations into vitamin E metabolism have also highlighted important new areas of research, such as the potential for high dose vitamin E supplementation to interfere with drug metabolism, as well as alternative methods to alter vitamin E bioavailability in vivo. These issues will also be discussed in the review.

Hypertension and oxidative stress

Publisher: Wiley

Date: 10-08-2006

DOI: 10.1111/J.1440-1681.2006.04457.X

Abstract: 1. Oxidative stress has been suggested to be involved in the pathogenesis of hypertension. This may be via a number of possible mechanisms, including quenching of the important vasodilator nitric oxide. 2. Animal studies have generally supported the hypothesis that increased blood pressure is associated with increased oxidative stress. However, human studies have been inconsistent and may differ owing to the populations studied and the various methods used. Treatment with anti-oxidants has been suggested to lower oxidative stress and, therefore, blood pressure. However, to date, studies investigating single or combination supplements have failed to show any consistent benefit. 3. Overall, the evidence supporting the link between hypertension and oxidative stress remains inconclusive, with methodological and population differences possibly confounding results. Further studies investigating this relationship are warranted.

Tea flavonoids and cardiovascular health

Publisher: Elsevier BV

Date: 12-2010

DOI: 10.1016/J.MAM.2010.09.004

Abstract: The two main types of tea are green and black. Both green and black teas are rich dietary sources of flavonoids. Available evidence suggests that regular tea consumption may reduce the risk of cardiovascular disease. The cardiovascular health benefits of drinking tea are thought to be largely due to flavonoids. Tea intake and intake of flavonoids found in tea have been associated with reduced risk of cardiovascular disease in cross-sectional and prospective population studies. Isolated flavonoids found in tea have also been consistently shown to inhibit the development of atherosclerosis in animal models. A number of possible pathways and mechanisms have been investigated. There is now consistent data indicating that tea and tea flavonoids can enhance nitric oxide status and improve endothelial function, which may be at least partly responsible for benefits on cardiovascular health. There is also evidence, although limited, to suggest benefits of green tea (flavonoids) on body weight and body fatness. Data supporting reduced oxidative damage, inflammation, platelet activation, blood pressure, and risk of type 2 diabetes with tea (flavonoids) remains inadequate to draw any conclusions.

Resolvins D1, D2, and other mediators of self-limited resolution of inflammation in human blood following n-3 fatty acid supplementation

Publisher: Oxford University Press (OUP)

Date: 10-2012

DOI: 10.1373/CLINCHEM.2012.190199

Abstract: Resolvins and protectins are families of local lipid mediators generated from the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) during self-limited resolution of inflammation. We aimed to develop a liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay to measure these lipid mediators in human blood following n-3 fatty acid supplementation and to determine whether the blood collection method affects their measured concentration. Blood s les from 20 healthy volunteers enrolled in an n-3 fatty acid supplementation trial were collected in EDTA, heparin, or citrate, or prepared as serum after volunteers had undergone 3 weeks of supplementation. Plasma or serum was purified by solid-phase chromatography and analyzed with LC-MS/MS. The assay identified 18R/S-hydroxy-5Z,8Z,11Z,14Z,16E-eicosapentaenoic acid (18R/S-HEPE) 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (17R/S-HDHA) 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid (RvD1) 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoicacid (17R-RvD1) 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid (RvD2) 10S,17S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoicacid (10S,17S-DiHDHA) and 10R,17S-dihydroxy-4Z,7Z,11E,13E,15Z,19Z-docosahexaenoic acid (protectin D1, PD1). The limits of detection and quantification were 3 pg and 6 pg on-column, respectively. The pathway precursors 18R/S-HEPE and 17R/S-HDHA, but not the resolvins, were lower in serum compared with plasma. After n-3 fatty acid supplementation, mean (SD) EDTA plasma concentrations were: 18R/S-HEPE 386 (56) pg/mL, 17R/S-HDHA 365 (65) pg/mL, RvD2 26 (4) pg/mL, RvD1 31 (5) pg/mL, and 17R-RvD 161 (7) pg/mL. 10S,17S-DiHDHA and PD1 concentrations were below the limit of quantification. This is the first study reporting 17R/S-HDHA, RvD1, and RvD2 concentrations measured in human blood following oral n-3 fatty acid supplementation. The concentrations of the antiinflammatory lipid mediators RvD1 and RvD2 were within the biological range known to have antiinflammatory and proresolving activities in isolated human leukocytes and in in vivo studies in mice.

Modulation of macrophage fatty acid content and composition by exposure to dyslipidemic serum in vitro.

Publisher: Wiley

Date: 02-2011

DOI: 10.1007/S11745-011-3528-2

Abstract: Macrophages in arterial walls accumulate lipids leading to the development of atherosclerotic plaques. However, mechanisms underlying macrophage lipid accumulation and foam cell formation are often studied without accounting for risk factors such as dyslipidemia. We investigated the effect of varying concentrations of triglyceride (TG) within physiological range on macrophage fatty acid (FA) accumulation and expression of cholesterol efflux proteins. Human monocytes were cultured in media supplemented with 10% sera containing low (0.7 mmol/L) to high (1.4 mmol/L) TG. The resulting macrophages were harvested after 10 days for analysis of FA content and composition and expression of genes involved in lipid metabolism. Exposure to higher TG and lower HDL concentrations in media increased macrophage lipid content. Macrophages exposed to higher TG had increased total FA content compared with controls (876 μg/mg protein vs. 652 μg/mg protein) and greater proportions of C16:0, C18:1 and C18:2. Macrophage expression of both ABCA1 and ABCG1 cholesterol efflux proteins were reduced when higher TG concentrations were present in the media. Expression of scavenger receptor CD36, involved in lipoprotein uptake, was also downregulated in macrophages exposed to higher TG. Culturing macrophages in conditions of higher versus lower TG influenced macrophage FA content and composition, and levels of regulatory proteins. Replicating in vitro levels of dyslipidemia encountered in vivo may provide an informative model for investigation of atherogenesis.

Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes

Publisher: Springer Science and Business Media LLC

Date: 11-2002

DOI: 10.1038/SJ.EJCN.1601464

Abstract: Our objective was to assess effects of dietary supplementation with coenzyme Q10 (CoQ) on blood pressure and glycaemic control in subjects with type 2 diabetes, and to consider oxidative stress as a potential mechanism for any effects. Seventy-four subjects with uncomplicated type 2 diabetes and dyslipidaemia were involved in a randomised double blind placebo-controlled 2x2 factorial intervention. The study was performed at the University of Western Australia, Department of Medicine at Royal Perth Hospital, Australia. Subjects were randomly assigned to receive an oral dose of 100 mg CoQ twice daily (200 mg/day), 200 mg fenofibrate each morning, both or neither for 12 weeks. We report an analysis and discussion of the effects of CoQ on blood pressure, on long-term glycaemic control measured by glycated haemoglobin (HbA(1c)), and on oxidative stress assessed by measurement of plasma F2-isoprostanes. Fenofibrate did not alter blood pressure, HbA(1c), or plasma F2-isoprostanes. There was a 3-fold increase in plasma CoQ concentration (3.4+/-0.3 micro mol/l, P<0.001) as a result of CoQ supplementation. The main effect of CoQ was to significantly decrease systolic (-6.1+/-2.6 mmHg, P=0.021) and diastolic (-2.9+/-1.4 mmHg, P=0.048) blood pressure and HbA(1c) (-0.37+/-0.17%, P=0.032). Plasma F2-isoprostane concentrations were not altered by CoQ (0.14+/-0.15 nmol/l, P=0.345). These results show that CoQ supplementation may improve blood pressure and long-term glycaemic control in subjects with type 2 diabetes, but these improvements were not associated with reduced oxidative stress, as assessed by F2-isoprostanes. This study was supported by a grant from the NH&MRC, Australia.

Higher habitual flavonoid intakes are associated with a lower risk of peripheral artery disease hospitalizations

Publisher: Elsevier BV

Date: 2021

DOI: 10.1093/AJCN/NQAA300

Nitrate

Publisher: Elsevier BV

Date: 05-2023

DOI: 10.1016/J.TIFS.2023.03.014

Polyphenol Composition of Plum Selections in Relation to Total Antioxidant Capacity

Publisher: American Chemical Society (ACS)

Date: 09-10-2012

DOI: 10.1021/JF302903K

Abstract: Dietary polyphenols are associated with protection against chronic diseases such as cardiovascular disease. Pharmacological studies show a range of bioactivities and efficacy attributable to specific polyphenols. While many fruits are rich in polyphenols, wide cultivar variation of polyphenol composition is common. Our objective was to determine the composition of major bioactive polyphenols in 29 prevarietal selections of Western Australian plums, and Black Amber as an evaluation in developing breeding tools to develop fruit that may have enhanced health-promoting capacities. Total phenolics were quantified colorimetrically selected polyphenols were quantified by HPLC and the total antioxidant capacity (TAC) was measured by the antioxidant inhibition of oxygen radicals (AIOR) assay. Total phenolic concentration was significantly correlated with TAC (R = 0.95, P < 0.01). Neo-chlorogenic acid and quercetin glycosides were found to be the predominant polyphenols (mean 29.9 mg·kg(-1) and 50.7 mg·kg(-1), respectively). No significant correlations were found between the composition of predominant polyphenols in plums and the TAC. We argue that the value of in vitro TAC assays to breeding programs may be limited, and future research should focus on the heritability of known bioactive polyphenols.

Quercetin and its metabolite isorhamnetin promote glucose uptake through different signalling pathways in myotubes

Publisher: Springer Science and Business Media LLC

Date: 25-02-2019

DOI: 10.1038/S41598-019-38711-7

Abstract: Quercetin and its metabolite isorhamnetin elicit various beneficial effects on human health. However, their bioavailability is low. In this study, we investigated whether low concentrations in the physiological range could promote glucose uptake in L6 myotubes, as well as the underlying molecular mechanisms. We found that 0.1 nM and 1 nM quercetin or 1 nM isorhamnetin significantly increased glucose uptake via translocation of glucose transporter type 4 (GLUT4) to the plasma membrane of L6 myotubes. Quercetin principally activated the CaMKKβ/AMPK signalling pathway at these concentrations, but also activated IRS1/PI3K/Akt signalling at 10 nM. In contrast, 1 nM and 10 nM isorhamnetin principally activated the JAK/STAT pathway. Treatment with siAMPKα and siJAK2 abolished quercetin- and isorhamnetin-induced GLUT4 translocation, respectively. However, treatment with siJAK3 did not affect isorhamnetin-induced GLUT4 translocation, indicating that isorhamnetin induced GLUT4 translocation mainly through JAK2, but not JAK3, signalling. Thus, quercetin preferably activated the AMPK pathway and, accordingly, stimulated IRS1/PI3K/Akt signalling, while isorhamnetin activated the JAK2/STAT pathway. Furthermore, after oral administration of quercetin glycoside at 10 and 100 mg/kg body weight significantly induced GLUT4 translocation to the plasma membrane of skeletal muscles in mice. In the same animals, plasma concentrations of quercetin aglycone form were 4.95 and 6.80 nM, respectively. In conclusion, at low-concentration ranges, quercetin and isorhamnetin promote glucose uptake by increasing GLUT4 translocation via different signalling pathways in skeletal muscle cells thus, these compounds may possess beneficial functions for maintaining glucose homeostasis by preventing hyperglycaemia at physiological concentrations.

Correction to Supplementation of a High-Fat Diet with Chlorogenic Acid Is Associated with Insulin Resistance and Hepatic Lipid Accumulation in Mice

Publisher: American Chemical Society (ACS)

Date: 09-02-2015

DOI: 10.1021/ACS.JAFC.5B00621

Development of a Vitamin K Database for Commercially Available Food in Australia

Publisher: Frontiers Media SA

Date: 09-12-2021

DOI: 10.3389/FNUT.2021.753059

Abstract: Vitamin K content of foods is known to vary substantially by geographical location. In Australia, no Vitamin K database of food exists, thereby creating ambiguity when trying to develop national dietary intake guidelines. This investigation aimed to develop a Vitamin K database for commonly consumed foods that are commercially available in Australian supermarkets. The Vitamin K1 (phylloquinone PK) and K2 (menaquinone MK4, MK7) content of 60 foods known to contain Vitamin K were assessed (e.g., vegetables fruits, oils, animal products, dairy and fermented foods). A liquid chromatography with tandem mass spectrometry (LCMS/MS) method was developed and used to measure PK and MKs in different foods with an improved chromatographic separation and detection of Vitamin K's and their analogs. The LOD and LOQ for PK and MK4 was 0.1, 0.5 ng/ml and 0.5, 1.0 ng/ml, respectively. The majority foods contained detectable PK (53/60), about half contained MK4 (31/60), and few contained MK7 (3/60). PK was highest in green leafy vegetables, with moderate amounts in oils. Highest MK4 content was in chicken eggs and meat products such as ham and chicken. This database enables nutritional epidemiologist to estimate dietary Vitamin K intake, especially in Australian cohorts, for a range of health outcomes.

Vitamin E in Human Health and Disease

Publisher: Informa UK Limited

Date: 2008

DOI: 10.1080/10408360802118625

Abstract: Vitamin E in nature is comprised of a family of tocopherols and tocotrienols. The most studied of these is alpha-tocopherol (alpha-TOH), because this form is retained within the body, and vitamin E deficiency is corrected with this supplement. alpha-TOH is a lipid-soluble antioxidant required for the preservation of cell membranes, and it potentially acts as a defense against oxidative stress. Many studies have investigated the metabolism, transport, and efficacy alpha-TOH in the prevention of sequelae associated with cardiovascular disease (CVD). Supplementation with vitamin E is considered to provide health benefits against CVD through its antioxidant activity, the prevention of lipoprotein oxidation, and the inhibition of platelet aggregation. However, the results from large prospective, randomized, placebo-controlled clinical trials with alpha-TOH have been largely negative. A recent meta-analysis suggests that alpha-TOH supplements may actually increase all-cause mortality however, the mechanism for this increased risk is unknown. In vitro studies performed in human cell cultures and animal models suggest that vitamin E might increase the hepatic production of cytochrome P450s and MDR1. Induction of CYP3A4 or MDR1 by vitamin E could potentially lower the efficacy of any drug metabolized by CYP3A4 or MDR1. Other possibilities include an adverse effect of alpha-TOH on blood pressure in high-risk populations. Because of the wide popularity and use of vitamin E supplements, further research into potential adverse effects is clearly warranted.

Angiotensin II type 1 receptor antagonists inhibit basal as well as low-density lipoprotein and platelet-activating factor-stimulated human monocyte chemoattractant protein-1.

Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)

Date: 06-03-2003

DOI: 10.1124/JPET.102.047795

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation

Publisher: Elsevier BV

Date: 11-2014

DOI: 10.1194/JLR.M045583

An examination of the effects of the antioxidant Pycnogenol® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population

Publisher: SAGE Publications

Date: 28-02-2008

DOI: 10.1177/0269881108091584

Abstract: The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly in iduals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60—85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group.

Low dose dietary nitrate improves endothelial dysfunction and plaque stability in the ApoE^−/−mouse fed a high fat diet

Publisher: Elsevier BV

Date: 10-2016

DOI: 10.1016/J.FREERADBIOMED.2016.08.009

Abstract: Nitric oxide (NO) is an important vascular signalling molecule. NO is synthesised endogenously by endothelial nitric oxide synthase (eNOS). An alternate pathway is exogenous dietary nitrate, which can be converted to nitrite and then stored or further converted to NO and used immediately. Atherosclerosis is associated with endothelial dysfunction and subsequent lesion formation. This is thought to arise due to a reduction in the bioavailability and/or bioactivity of endogenous NO. To determine if dietary nitrate can protect against endothelial dysfunction and lesion formation in the ApoE ApoE Low and moderate dose nitrate significantly improved endothelial function and atherosclerotic plaque composition in ApoE

Effects of vitamin E, vitamin C and polyphenols on the rate of blood pressure variation: Results of two randomised controlled trials

Publisher: Cambridge University Press (CUP)

Date: 19-09-2014

DOI: 10.1017/S0007114514002542

Abstract: High blood pressure (BP) variability, which may be an important determinant of hypertensive end-organ damage, is emerging as an important predictor of cardiovascular health. Dietary antioxidants can influence BP, but their effects on variability are yet to be investigated. The aim of the present study was to assess the effects of vitamin E, vitamin C and polyphenols on the rate of daytime and night-time ambulatory BP variation. To assess these effects, two randomised, double-blind, placebo-controlled trials were performed. In the first trial (vitamin E), fifty-eight in iduals with type 2 diabetes were given 500 mg/d of RRR -α-tocopherol, 500 mg/d of mixed tocopherols or placebo for 6 weeks. In the second trial (vitamin C–polyphenols), sixty-nine treated hypertensive in iduals were given 500 mg/d of vitamin C, 1000 mg/d of grape-seed polyphenols, both vitamin C and polyphenols, or neither (placebo) for 6 weeks. At baseline and at the end of the 6-week intervention, 24 h ambulatory BP and rate of measurement-to-measurement BP variation were assessed. Compared with placebo, treatment with α-tocopherol, mixed tocopherols, vitamin C and polyphenols did not significantly alter the rate of daytime or night-time systolic BP, diastolic BP or pulse pressure variation ( P ·05). Treatment with the vitamin C and polyphenol combination resulted in higher BP variation: the rate of night-time systolic BP variation ( P = 0·022) and pulse pressure variation ( P = 0·0036) were higher and the rate of daytime systolic BP variation was higher ( P = 0·056). Vitamin E, vitamin C or grape-seed polyphenols did not significantly alter the rate of BP variation. However, the increase in the rate of BP variation suggests that the combination of high doses of vitamin C and polyphenols could be detrimental to treated hypertensive in iduals.

Novel relationships between B12, folate and markers of inflammation, oxidative stress and NAD(H) levels, systemically and in the CNS of a healthy human cohort

Publisher: Informa UK Limited

Date: 11-08-2015

DOI: 10.1179/1476830515Y.0000000041

Supplementation with Grape Seed Polyphenols Results in Increased Urinary Excretion of 3-Hydroxyphenylpropionic Acid, an Important Metabolite of Proanthocyanidins in Humans

Publisher: American Chemical Society (ACS)

Date: 24-07-2004

DOI: 10.1021/JF049404R

Abstract: Grape seed extract provides a concentrated source of polyphenols, most of which are proanthocyanidins. Polymeric proanthocyanidins are poorly absorbed in the small intestine of humans, and exposure may result from metabolism to phenolic acids by colonic bacteria. Any biological effects of proanthocyanidins may be due to the phenolic acid metabolites. Several phenolic acids have been identified as proanthocyanidin metabolites, but these may be derived from a range of other dietary sources. The aim of this study was to determine if 24-h urinary excretion of specific phenolic acids increased significantly and consistently following regular supplementation with grape seed extract. In a randomized, double-blind placebo-controlled trial, 69 volunteers received grape seed extract (1000 mg/day total polyphenols) or placebo for 6 weeks. Supplementation with grape seed polyphenols resulted in a consistent increase in the excretion of 3-hydroxyphenylpropionic acid (3-HPP, P < 0.001) and 4-O-methylgallic acid (P < 0.001) and a less consistent increase in the excretion of 3-hydroxyphenylacetic acid (P = 0.002). The observed increase in 3-HPP is in line with the suggestion that this compound is a major phenolic acid breakdown product of proanthocyanidin metabolism in vivo.

Mechanisms of the protective effects of nitrate and nitrite in cardiovascular and metabolic diseases

Publisher: Elsevier BV

Date: 03-2020

DOI: 10.1016/J.NIOX.2020.01.006

Abstract: Within the body, NO is produced by nitric oxide synthases via converting

The Relationship between F₂-Isoprostanes Plasma Levels and Depression Symptoms in Healthy Older Adults

Publisher: MDPI AG

Date: 22-04-2022

DOI: 10.3390/ANTIOX11050822

Abstract: The increasing proportion of older citizens in our society reflects a need to better understand age-related biological underpinnings of mood, as depression in older age may be under-diagnosed. Pre-clinical and human studies evidence a relationship between oxidative stress (OS) biomarkers in depression symptoms, and an influence of biological factors such as Body Mass Index (BMI), but focus has been clinical or younger s les, and less is known about patterns in healthy older adults. We investigated these associations with data derived from the Australian Research Council Longevity Study (ARCLI ANZCTR12611000487910), in 568 healthy adults aged 60–75 years using F2-Isoprostanes plasma levels, and controlling for demographic factors, in assessing mood via the Beck Depression Inventory-II, Chalder Fatigue Scale, and General Health Questionnaire 12. Elevated F2-Isoprostanes contributed to depressed mood on the BDI-II and reduced general health on the GHQ-12. BMI was positively associated with Chalder Fatigue scores, yet better ratings on the GHQ-12. Females had significantly higher F2-Isoprostanes than males. The results suggest that in otherwise healthy older adults, mood and mental health are reduced with increases in oxidative stress markers, exhibiting similar patterns observed in clinical groups. Sex as a factor should be considered when assessing OS levels in systemic pathologies. BMI as a modifiable risk factor for maintenance of mental health, and OS modification through nutrient supplementation, are discussed. The findings contribute to understanding oxidative stress marker patterns in healthy older adults and their potential role in mood symptoms and mental health.

Effects of black tea on blood pressure: A randomized controlled trial

Publisher: American Medical Association (AMA)

Date: 23-01-2012

DOI: 10.1001/ARCHINTE.172.2.186

The Acute Effects of Quercetin-3-O-Glucoside on Endothelial Function and Blood Pressure

Publisher: Elsevier BV

Date: 06-2017

DOI: 10.1016/J.JNIM.2017.04.161

Altered expression of nuclear factor-κB in peripheral blood mononuclear cells in chronic haemodialysis patients [17]

Publisher: Oxford University Press (OUP)

Date: 06-12-2006

DOI: 10.1093/NDT/GFI258

Apocynin but Not Allopurinol Prevents and Reverses Adrenocorticotropic Hormone-Induced Hypertension in the Rat

Publisher: Oxford University Press (OUP)

Date: 07-2005

DOI: 10.1016/J.AMJHYPER.2005.02.017

Abstract: Adrenocorticotropic hormone (ACTH)-induced hypertension in the rat is accompanied by increased oxidative stress. This study examines the enzymatic source of reactive oxygen species in ACTH-hypertension. Male Sprague-Dawley rats were ided into 10 groups of 10-20 rats per group. The NAD(P)H oxidase inhibitor apocynin (1.5 mmol/L in drinking water) or the xanthine oxidase inhibitor allopurinol (200 mg/kg/day via food) were administered daily. After 4 days, rats were co-administered ACTH (0.2 mg/kg/day) or saline by subcutaneous injection daily for 11 days (prevention study). In a reversal study, ACTH/saline was administered for 13 days and from day 8, apocynin or allopurinol was added for 5 days. Systolic blood pressure (SBP) was measured by the tail-cuff method and oxidative stress using plasma F2-isoprostane concentrations. Results were expressed as mean+/-SEM. ACTH increased SBP (P<.001) but apocynin or allopurinol alone had no effect. Apocynin (but not allopurinol) co-treatment prevented (142+/-3 ACTH, 120+/-4 mm Hg apocynin+ACTH, P'<0.001) and reversed ACTH-induced hypertension (133+/-4 to 118+/-5 mm Hg, P<.05). Plasma F2-isoprostane concentrations were increased in ACTH-treated rats compared with saline (11.9+/-1.0 vs 8.2+/-0.8 nmol/L, P<.01), and apocynin attenuated the ACTH-induced rise in plasma F2-isoprostane concentrations. Serum urate concentrations were undetectable in 75% of rats treated with allopurinol and were not affected by ACTH. Apocynin but not allopurinol prevented and reversed ACTH-induced hypertension in the rat. These results suggest superoxide production through NAD(P)H oxidase plays a role in ACTH-induced hypertension.

The anti-oxidant Tempol reverses and partially prevents adrenocorticotrophic hormone-induced hypertension in the rat

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 08-2003

DOI: 10.1097/00004872-200308000-00015

Abstract: To investigate the effects of the antioxidant Tempol on prevention and reversal of adrenocorticotrophic hormone (ACTH)-induced hypertension in the rat, a model of hypertension characterized by nitric oxide deficiency. Male Sprague-Dawley rats (n = 10 in each group) were treated with either saline or ACTH (0.2 mg/kg per day, s.c.) for 12 days. Tempol (1 mmol/l in drinking water) treatment was started on either day 8 (T8) of ACTH or saline treatment (reversal study), or 4 days prior to ACTH or saline treatment (prevention study). Systolic blood pressure (SBP) was measured using tail-cuff sphygmomanometry. Plasma F2-isoprostanes, a marker of oxidative stress, were measured by gas chromatography-mass spectrometry. ACTH increased SBP (mean +/- SEM: 119 +/- 5 to 147 +/- 7 mmHg, P < 0.0005) and plasma F2-isoprostane concentration (8.4 +/- 1.2 saline versus 12.9 +/- 1.6 nmol/l ACTH, P < 0.05). Tempol alone did not alter SBP, but administration of Tempol on T8 reversed ACTH-induced hypertension (from 134 +/- 4 T8 to 118 +/- 3 mmHg, P < 0.005). Tempol pre-treatment partially prevented ACTH-induced hypertension (123 +/- 2 mmHg, P' < 0.05). However, Tempol had no effect on F2-isoprostane concentrations at the dose used in this study. ACTH-induced hypertension in the rat is associated with increased oxidative stress. Tempol treatment reversed, and pretreatment partially prevented ACTH-induced hypertension, independent of improvement in systemic oxidative stress.

The combination of vitamin C and grape-seed polyphenols increases blood pressure: A randomized, double-blind, placebo-controlled trial

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 02-2005

DOI: 10.1097/00004872-200502000-00026

Abstract: There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension and endothelial dysfunction. Thus, dietary antioxidants may beneficially influence blood pressure (BP) and endothelial function by reducing oxidative stress. To determine if vitamin C and polyphenols, alone or in combination, can lower BP, improve endothelial function and reduce oxidative stress in hypertensive in iduals. A total of 69 treated hypertensive in iduals with a mean 24-h ambulatory systolic blood pressure > or = 125 mmHg participated in a randomized, double-blind, placebo-controlled, factorial trial. Following a 3-week washout, participants received 500 mg/day vitamin C, 1000 mg/day grape-seed polyphenols, both vitamin C and polyphenols, or neither for 6 weeks. At baseline and post-intervention, 24-h ambulatory BP, ultrasound-assessed endothelium-dependent and -independent vasodilation of the brachial artery, and markers of oxidative damage, (plasma and urinary F2-isoprostanes, oxidized low-density lipoproteins and plasma tocopherols), were measured. A significant interaction between grape-seed and vitamin C treatments for effects on BP was observed. Vitamin C alone reduced systolic BP versus placebo (-1.8 +/- 0.8 mmHg, P = 0.03), while polyphenols did not (-1.3 +/- 0.8 mmHg, P = 0.12). However, treatment with the combination of vitamin C and polyphenols increased systolic BP (4.8 +/- 0.9 mmHg versus placebo 6.6 +/- 0.8 mmHg versus vitamin C 6.1 +/- 0.9 mmHg versus polyphenols mmHg, each P < 0.0001) and diastolic BP (2.7 +/- 0.6 mmHg, P < 0.0001 versus placebo 1.5 +/- 0.6 mmHg, P = 0.016 versus vitamin C 3.2 +/- 0.7 mmHg, P < 0.0001 versus polyphenols). Endothelium-dependent and -independent vasodilation, and markers of oxidative damage were not significantly altered. Although the mechanism remains to be elucidated, these results suggest caution for hypertensive subjects taking supplements containing combinations of vitamin C and polyphenols.

Randomized controlled trial examining the effects of fish oil and multivitamin supplementation on the incorporation of n-3 and n-6 fatty acids into red blood cells

Publisher: MDPI AG

Date: 14-05-2014

DOI: 10.3390/NU6051956

Measurement of 20-Hydroxyeicosatetraenoic Acid in Human Urine by Gas Chromatography-Mass Spectrometry

Publisher: Oxford University Press (OUP)

Date: 2004

DOI: 10.1373/CLINCHEM.2003.025775

Folic acid Prevents and Partially Reverses Glucocorticoid- Induced Hypertension in the Rat

Publisher: Oxford University Press (OUP)

Date: 03-2007

DOI: 10.1016/J.AMJHYPER.2006.08.007

Abstract: To investigate the effect of folic acid on the increased pressure in rats treated with either adrenocorticotropic hormone (ACTH) or dexamethasone (Dex), and to further investigate the role of tetrahydrobiopterin (BH(4)) in any effect of folic acid by comparing the effect of BH(4) with that of folic acid in Dex hypertension. Male Sprague-Dawley (SD) rats were treated with saline, subcutaneous ACTH (0.2 mg/kg/d) or Dex (10 microg/rat/d). Folic acid (0.04 g/L drinking) or BH(4) (10 mg/kg/d intraperitoneally) was started before (prevention) and during (reversal) glucocorticoid treatment. Saline, BH(4), vehicle for BH(4), or folic acid alone did not change systolic blood pressure (BP). Systolic BP was increased by ACTH and Dex. Folic acid, but not BH(4), prevented the development of hypertension caused by ACTH and Dex treatment. The ACTH and Dex hypertension were partially reversed by folic acid. The BH(4) increased plasma total biopterin concentrations. The Dex decreased plasma NOx concentrations but had no effect on plasma biopterin concentrations. The ACTH and Dex increased plasma F(2)-isoprostane concentrations and decreased serum homocysteine concentrations compared with control but had no effect on serum folate concentrations. Folic acid increased serum folate concentrations compared with control but had no effect on homocysteine concentrations. Folic acid prevented and partially reversed both ACTH and Dex hypertension in rats without modifying the increase in plasma F(2)-isoprostane concentrations. Given that BH(4) failed to prevent ACTH or Dex hypertension, folic acid is unlikely to be acting through increased BH(4) production. The precise mechanism for the BP-lowering effect of folic acid in this model of hypertension remains to be determined.

The Relationship between Oxidative Stress and Anxiety in a Healthy Older Population

Publisher: Informa UK Limited

Date: 20-02-2021

DOI: 10.1080/0361073X.2021.1883966

Isoquercetin and inulin synergistically modulate the gut microbiome to prevent development of the metabolic syndrome in mice fed a high fat diet

Publisher: Springer Science and Business Media LLC

Date: 04-07-2018

DOI: 10.1038/S41598-018-28521-8

Abstract: Dietary fibre positively influences gut microbiome composition, enhancing the metabolism of dietary flavonoids to produce bioactive metabolites. These synergistic activities facilitate the beneficial effects of dietary flavonoids on cardiometabolic health parameters. The aims of this study were to investigate whether isoquercetin (a major dietary flavonoid) and inulin (soluble fibre), either alone or in combination could improve features of the metabolic syndrome. Following a 1 week acclimatization, male C57BL6 mice (6–8 weeks) were randomly assigned to (i) normal chow diet (n = 10), (ii) high fat (HF) diet (n = 10), (iii) HF diet + 0.05% isoquercetin (n = 10), (iv) HF diet + 5% inulin, or (v) HF diet + 0.05% isoquercetin + 5% inulin (n = 10). Body weight and food intake were measured weekly. At 12 weeks, glucose and insulin tolerance tests were performed, and blood, faecal s les, liver, skeletal muscle and adipose tissue were collected. At 12 weeks, mice on the HF diet had significantly elevated body weights as well as impaired glucose tolerance and insulin sensitivity compared to the normal chow mice. Supplementation with either isoquercetin or inulin had no effect, however mice receiving the combination had attenuated weight gain, improved glucose tolerance and insulin sensitivity, reduced hepatic lipid accumulation, adipocyte hypertrophy, circulating leptin and adipose FGF21 levels, compared to mice receiving the HF diet. Additionally, mice on the combination diet had improvements in the composition and functionality of their gut microbiome as well as production of short chain fatty acids. In conclusion, long-term supplementation with the dietary flavonoid isoquercetin and the soluble fibre inulin can attenuate development of the metabolic syndrome in mice fed a high fat diet. This protective effect appears to be mediated, in part, through beneficial changes to the microbiome.

Inhibition of MPO (Myeloperoxidase) Attenuates Endothelial Dysfunction in Mouse Models of Vascular Inflammation and Atherosclerosis

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2019

DOI: 10.1161/ATVBAHA.119.312725

Abstract: Inflammation-driven endothelial dysfunction initiates and contributes to the progression of atherosclerosis, and MPO (myeloperoxidase) has been implicated as a potential culprit. On release by circulating phagocytes, MPO is thought to contribute to endothelial dysfunction by limiting NO bioavailability via formation of reactive oxidants including hypochlorous acid. However, it remains largely untested whether specific pharmacological inhibition of MPO attenuates endothelial dysfunction. We, therefore, tested the ability of a mechanism-based MPO inhibitor, AZM198, to inhibit endothelial dysfunction in models of vascular inflammation. Three models of inflammation were used: femoral cuff, the tandem stenosis model of plaque rupture in Apoe −/− mice, and C57BL/6J mice fed a high-fat, high-carbohydrate diet as a model of insulin resistance. Endothelial dysfunction was observed in all 3 models, and oral administration of AZM198 significantly improved endothelial function in the femoral cuff and tandem stenosis models only. Improvement in endothelial function was associated with decreased arterial MPO activity, determined by the in vivo conversion of hydroethidine to 2-chloroethidium, without affecting circulating inflammatory cytokines or arterial MPO content. Mechanistic studies in Mpo −/− mice confirmed the contribution of MPO to endothelial dysfunction and revealed oxidation of sGC (soluble guanylyl cyclase) as the underlying cause of the observed limited NO bioavailability. Pharmacological inhibition of MPO is a potential strategy to limit endothelial dysfunction in vascular inflammation. An online visual overview is available for this article.

Endothelial cationic amino acid transporter-1 overexpression can prevent oxidative stress and increases in arterial pressure in response to superoxide dismutase inhibition in mice

Publisher: Wiley

Date: 16-01-2014

DOI: 10.1111/APHA.12215

Abstract: Oxidative stress may play an important role in the pathogenesis of hypertension. The aim of our study is to examine whether increased expression of the predominant endothelial l-arginine transporter, cationic amino acid transporter-1 (CAT1), can prevent oxidative stress-induced hypertension. Wild-type mice (WT n = 9) and endothelial CAT1 overexpressing (CAT+) mice (n = 6) had telemetry probes implanted for the measurement of mean arterial pressure (MAP), heart rate (HR) and locomotor activity. Minipumps were implanted for infusion of the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETCA 30 mg kg(-1) day(-1) 14 days) or its saline vehicle. Baseline levels of MAP, HR and locomotor activity were determined before and during chronic DETCA administration. Mice were then killed, and their plasma and kidneys collected for analysis of F2 -isoprostane levels. Basal MAP was less in CAT+ (92 ± 2 mmHg n = 6) than in WT (98 ± 2 mmHg n = 9 P < 0.001). During DETCA infusion, MAP was increased in WT (by 4.2 ± 0.5% P < 0.001) but not in CAT+, when compared to appropriate controls (PDETCA*genotype = 0.006). DETCA infusion increased total plasma F2 -isoprostane levels (by 67 ± 11% P = 0.05) in WT but not in CAT+. Total renal F2 -isoprostane levels were greater during DETCA infusion in WT (by 72% P < 0.001), but not in CAT+, compared to appropriate controls. Augmented endothelial l-arginine transport attenuated the prohypertensive effects of systemic and renal oxidative stress, suggesting that manipulation of endothelial CAT1 may provide a new therapeutic approach for the treatment of cardiovascular disease associated with oxidative stress.

Similarity in the distribution of F2 -isoprostanes in the lipid subfractions of atherosclerotic plaque and in vitro oxidised low density lipoprotein

Publisher: Informa UK Limited

Date: 06-2002

DOI: 10.1179/135100002125000433

Abstract: Oxidation of low density lipoprotein (LDL) in vivo is thought to play a critical role in the initiation of atherosclerosis. F(2)-isoprostanes are compounds resulting from non-enzymatic oxidation of arachidonic acid and elevated levels are present in human atherosclerotic plaque. However, little is known about the formation of F(2)-isoprostanes in plaque lesions or their distribution in lipid subclasses. Given that LDL and tissue lipid subfractions (such as phospholipids, cholesterol esters and triglycerides) all contain significant levels of arachidonic acid, the aim of this study was to examine the relative distribution of F(2)-isoprostanes in the different lipid fractions of LDL oxidised in vitro, and compare this to the distribution in atherosclerotic plaque. The results reveal that while the majority of F(2)-isoprostanes are present in the phospholipid or surface lipid fractions, the core lipids (cholesterol esters/triglycerides) contribute at least 10% of the total F(2)-isoprostanes in both LDL oxidised in vitro and human atherosclerotic plaque. The remarkably similar profiles between the oxidised LDL and advanced atherosclerotic plaque suggests oxidation in vivo, is predominantly via non-enzymatic processes directed towards the surface lipids.

Quantifying dietary vitamin K and its link to cardiovascular health: a narrative review

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/C9FO02321F

Abstract: Potential beneficial pathways by which vitamin K may reduce the risk of cardiovascular disease mortality.

Supplementation of a High-Fat Diet with Chlorogenic Acid Is Associated with Insulin Resistance and Hepatic Lipid Accumulation in Mice

Publisher: American Chemical Society (ACS)

Date: 26-04-2013

DOI: 10.1021/JF400920X

Abstract: The increasing prevalence of the metabolic syndrome requires a greater need for therapeutic and prevention strategies. Higher coffee consumption is consistently associated with a lower risk of type 2 diabetes in population studies. Dietary polyphenols have been linked to benefits on several features of the metabolic syndrome. Chlorogenic acid (CGA), a major component of coffee, is one of the most consumed polyphenols in the diet. In our study, we conducted a controlled dietary intervention over 12 weeks in male mice. There were three dietary groups: (i) normal diet, (ii) high-fat diet, and (iii) high-fat diet + CGA. We assessed the effect of CGA at a physiologically obtainable dose (1 g/kg of diet) on high-fat-diet-induced obesity, glucose intolerance, insulin resistance, and also fatty acid oxidation and insulin signaling in C57BL/6 male mice. Supplementation of CGA in the high-fat diet did not reduce body weight compared to mice fed the high-fat diet alone (p = 0.32). CGA resulted in increased insulin resistance compared to mice fed a high-fat diet only (p < 0.05). CGA resulted in decreased phosphorylation of AMP-activated protein kinase (AMPK) (p < 0.001) and acetyl carboxylase β (ACCβ), a downstream target of AMPK (p < 0.05), in liver. The liver of mice fed a high-fat diet supplemented with CGA had a higher lipid content (p < 0.05) and more steatosis relative to mice fed a high-fat diet only, indicating impaired fatty acid oxidation. This study suggests that CGA supplementation in a high-fat diet does not protect against features of the metabolic syndrome in diet-induced obese mice.

A Metabolite Profiling Approach to Identify Biomarkers of Flavonoid Intake in Humans

Publisher: Elsevier BV

Date: 12-2009

DOI: 10.3945/JN.109.113613

Abstract: Flavonoids are phytochemicals that are widespread in the human diet. Despite limitations in their bioavailability, experimental and epidemiological data suggest health benefits of flavonoid consumption. Valid biomarkers of flavonoid intake may be useful for estimating exposure in a range of settings. However, to date, few useful flavonoid biomarkers have been identified. In this study, we used a metabolite profiling approach to examine the aromatic and phenolic profile of plasma and urine of healthy men after oral consumption of 200 mg of the pure flavonoids, quercetin, (-)-epicatechin, and epigallocatechin gallate, which represent major flavonoid constituents in the diet. Following enzymatic hydrolysis, 71 aromatic compounds were quantified in plasma and urine at 2 and 5 h, respectively, after flavonoid ingestion. Plasma concentrations of different aromatic compounds ranged widely, from 0.01 to 10 micromol/L, with variation among volunteers. None of the aromatic compounds was significantly elevated in plasma 2 h after consumption of either flavonoid compared with water placebo. This indicates that flavonoid-derived aromatic compounds are not responsible for the acute physiological effects reported within 2 h in previous human intervention studies involving flavonoids or flavonoid-rich food consumption. These effects are more likely due to absorption of the intact flavonoid. Our urine analysis suggested that urinary 4-ethylphenol, benzoic acid, and 4-ethylbenzoic acid may be potential biomarkers of quercetin intake and 1,3,5-trimethoxybenzene, 4-O-methylgallic acid, 3-O-methylgallic acid, and gallic acid may be potential markers of epigallocatechin gallate intake. Potential biomarkers of (-)-epicatechin were not identified. These urinary biomarkers may provide an accurate indication of flavonoid exposure.

Low density lipoprotein composition and oxidizability in coronary disease - Apparent favourable effect of beta blockers

Publisher: Elsevier BV

Date: 12-1992

DOI: 10.1016/0021-9150(92)90125-Z

Abstract: The oxidative modification of LDL in vivo may have an important role in atherogenesis. To determine whether LDL fatty acid, anti-oxidant composition and sensitivity to oxidation in vitro is different in subjects with established atherosclerosis we compared 20 men with angiogram proven coronary disease with 25 controls without clinical evidence of arterial disease. LDL-cholesterol, total triglycerides and LDL fatty acid composition did not differ significantly between the groups. LDL oxidation lag time and oxidation rate in coronary patients (132 min, 0.02 absorbance units/min) and controls (140, 0.017) were not significantly different. However coronary disease subjects taking beta-blockers had evidence for reduced LDL oxidizability (lag time 148 +/- 7 min oxidation rate 0.017 +/- 0.002 abs units/min) compared with those not on beta-blockers (lag time 114 +/- 7 min, rate 0.025 +/- 0.003, P < 0.005). LDL beta-carotene was significantly lower in coronary patients (0.92 mumol/mmol LDL cholesterol controls 1.58 P = 0.001). LDL alpha-tocopherol appeared lower in coronary patients (2.8 mumol/mmol LDL cholesterol controls 3.3 P = 0.056) and was significantly lower in smokers (2.56 non-smokers 3.24 P = 0.04). LDL oxidation rate was negatively correlated with LDL alpha-tocopherol (r = -0.51, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Bioavailability of phenolic compounds and antioxidant effects of wine pomace seasoning after oral administration in rats

Publisher: Elsevier BV

Date: 08-2016

DOI: 10.1016/J.JFF.2016.06.030

20-Hydroxyeicosatetraenoic acid is not associated with circulating insulin in lean to overweight humans

Publisher: Elsevier BV

Date: 11-2006

DOI: 10.1016/J.DIABRES.2006.04.001

Abstract: Hypertension is often associated with insulin resistance or hyperinsulinemia. Metabolism of arachidonic acid by cytochrome P450 to the vasoconstrictor 20-HETE is thought to be involved in the pathogenesis of hypertension, but the relationship of 20-HETE with insulin resistance is not clearly understood. Obesity is a major determinant of insulin resistance, and we have previously demonstrated a positive relationship between BMI and 20-HETE in untreated hypertensive and normotensive in iduals. The present analysis sought to determine if this relationship was related to insulin levels or insulin resistance (HOMA). We analysed 24h urinary excretion of 20-HETE, serum insulin levels and insulin resistance in 66 lean to overweight untreated hypertensive and normotensive in iduals. There was a significant positive association between 20-HETE and BMI (p<0.001), and serum insulin and BMI (p=0.003). There were no associations between 20-HETE excretion and either serum insulin or insulin resistance, before or after adjustment for age, gender, BMI and BP, or when hypertensive and normotensive in iduals were considered separately. The results of the present study suggest that the observed positive association between urinary 20-HETE excretion and BMI may not be related to circulating insulin levels or insulin resistance.

Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: A randomized controlled trial

Publisher: Elsevier BV

Date: 2012

DOI: 10.1016/J.FREERADBIOMED.2011.09.028

Abstract: Flavonoids and nitrates in fruits and vegetables may protect against cardiovascular disease. Dietary flavonoids and nitrates can augment nitric oxide status via distinct pathways, which may improve endothelial function and lower blood pressure. Recent studies suggest that the combination of flavonoids and nitrates can enhance nitric oxide production in the stomach. Their combined effect in the circulation is unclear. Here, our objective was to investigate the independent and additive effects of flavonoid-rich apples and nitrate-rich spinach on nitric oxide status, endothelial function, and blood pressure. A randomized, controlled, crossover trial with healthy men and women (n=30) was conducted. The acute effects of four energy-matched treatments (control, apple, spinach, and apple+spinach), administered in random order, were compared. Measurements included plasma nitric oxide status, assessed by measuring S-nitrosothiols+other nitrosylated species (RXNO) and nitrite, blood pressure, and endothelial function, measured as flow-mediated dilatation of the brachial artery. Results are means and 95% CI. Relative to control, all treatments resulted in higher RXNO (control, 33 nmol/L, 26, 42 apple, 51 nmol/L, 40, 65 spinach, 86 nmol/L, 68, 110 apple+spinach, 69 nmol/L, 54, 88 P<0.01) and higher nitrite (control, 35 nmol/L, 27, 46 apple, 69 nmol/L, 53, 90 spinach, 99 nmol/L, 76, 129 apple+spinach, 80 nmol/L, 61, 104 P<0.01). Compared to control, all treatments resulted in higher flow-mediated dilatation (P<0.05) and lower pulse pressure (P<0.05), and apple and spinach resulted in lower systolic blood pressure (P<0.05). No significant effect was observed on diastolic blood pressure. The combination of apple and spinach did not result in additive effects on nitric oxide status, endothelial function, or blood pressure. In conclusion, flavonoid-rich apples and nitrate-rich spinach can independently augment nitric oxide status, enhance endothelial function, and lower blood pressure acutely, outcomes that may benefit cardiovascular health.

The cardiovascular health benefits of apples: Whole fruit vs. isolated compounds

Publisher: Elsevier BV

Date: 11-2017

DOI: 10.1016/J.TIFS.2017.04.012

Direct association between the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 and plasma mevalonic acid and lathosterol concentrations in man

Publisher: Elsevier BV

Date: 11-1997

DOI: 10.1016/S0021-9150(97)00153-6

Abstract: Apolipoprotein B-100 (apo B) is the principal structural and functional protein of the pro-atherogenic lipoproteins, but its homeostasis in man has not been clearly established. The hepatic availability of cholesterol substrate may be a determining factor. We examined whether there was a direct correlation between plasma concentrations of mevalonic acid (MVA) and lathosterol (indices of in vivo cholesterol synthesis) and hepatic secretion of very-low-density lipoprotein (VLDL) apo B in 13 normolipidaemic, healthy male subjects. The secretion of VLDL apo B was measured using a primed constant intravenous infusion of 1-[13C]-leucine (1 mg/kg per h) over 8 h. Gas-chromatography mass spectrometry (GCMS) was used to derive isotopic enrichment of apo B and fractional turnover rate was calculated using a monoexponential function. There was a highly significant positive correlation between the absolute secretion rate (ASR) of VLDL apo B and the plasma concentrations of mevalonic acid (r = 0.72, P = 0.005) and lathosterol (r = 0.81, P = 0.001) and the lathosterol:cholesterol ratio (r = 0.79, P = 0.001). In multiple regression analysis, these correlations remained significant after adjusting for waist circumference, age, apolipoprotein E genotype and dietary fat intake. The data further support the notion that the availability of cholesterol substrate regulates the hepatic secretion rate of apo B.

Flavonoid intake and its association with atrial fibrillation

Publisher: Elsevier BV

Date: 12-2020

DOI: 10.1016/J.CLNU.2020.04.025

Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation

Publisher: American Chemical Society (ACS)

Date: 05-2008

DOI: 10.1021/JF8003042

Abstract: This study examined the effects of metabolic transformation of the common dietary flavonoid, quercetin, on its ability to protect low-density lipoprotein (LDL) from neutrophil-mediated modification. Quercetin was shown to be effective in protecting LDL against neutrophil-mediated modification at physiological concentrations (1 microM) and appears to act by inhibiting myeloperoxidase (MPO)-catalyzed oxidation (IC(50) = 1.0 microM). Quercetin was also shown to protect against radical-induced [2,2'-azobis(2-methylpropionamidine)dihydrochloride] oxidation (IC(50) = 1.5 microM). Studies of structure-activity relationships showed that methylation at the 3'-position or glucuronidation at the 3-position did not significantly affect inhibition by quercetin of the MPO activity, but conjugations at both positions significantly reduce its activity. Our results suggest that the common dietary flavonoid, quercetin, and some of its major in vivo metabolites are potential inhibitors of MPO at physiological concentrations. Dietary flavonoids that could modify MPO activity could protect lipoproteins from damage in chronic inflammatory states such as cardiovascular disease.

Polyphenols and health

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/D0FO90042G

Abstract: Kevin Croft and Cesar Fraga introduce the Food & Function themed collection for the International Conference on Polyphenols and Health (ICPH2019).

Dietary Iron Enhances Colonic Inflammation and IL-6/IL-11-Stat3 Signaling Promoting Colonic Tumor Development in Mice

Publisher: Public Library of Science (PLoS)

Date: 06-11-2013

DOI: 10.1371/JOURNAL.PONE.0078850

Association between both lipid and protein oxidation and the risk of fatal or non-fatal coronary heart disease in a human population.

Publisher: Portland Press Ltd.

Date: 28-11-2009

DOI: 10.1042/CS20070404

Abstract: The role of oxidative damage in the aetiology of coronary disease remains controversial, as clinical trials investigating the effect of antioxidants have not generally been positive. In the present study, 227 coronary cases, identified from a cohort study, were matched, by age and gender, with 420 controls in a nested case-control design. Stored plasma s les were analysed for F2-isoprostanes by stable isotope dilution MS, and specifically oxidized forms of apoA-I (apolipoprotein A-I) by HPLC of HDL (high-density lipoprotein). Median values of F2-isoprostanes were higher in plasma s les that contained oxidized apoA-I compared with s les with undetectable oxidized apoA-I (1542 compared with 1165 pmol/l). F2-Isoprostanes were significantly correlated with variants of non-oxidized apoA-II (r=−0.15) and were associated with HDL-cholesterol (P& .0001). F2-Isoprostanes in cases (median, 1146 pmol/l) were not different from controls (1250 pmol/l) the odds ratio (95% confidence interval) for a 1 S.D. increase in F2-isoprostanes was 1.08 (0.91–1.29). Similarly, there was no independent association between the presence of oxidized apoA-I, detected in approx. 20% of the s les, and coronary risk. In conclusion, we found no evidence of associations between markers of lipid (F2-isoprostanes) and protein (oxidized apoA-I) oxidation and the risk of fatal or non-fatal coronary heart disease in a general population. This may be due to a true lack of association or insufficient power.

Effects of Isoflavonoids on blood pressure in subjects with high-normal ambulatory blood pressure levels

Publisher: Oxford University Press (OUP)

Date: 1999

DOI: 10.1016/S0895-7061(98)00216-7

Abstract: Vegetarian diets lower blood pressure (BP), but attempts to identify dietary components responsible have been unsuccessful. Isoflavonoids are commonly consumed as part of vegetarian diets. The objective of this study was to assess the effect of isoflavonoid supplementation on BP. Fifty-nine subjects with high-normal range systolic BP completed a randomized, double blind, placebo-controlled trial of two-way parallel design and 8 weeks duration. One tablet containing 55 mg of isoflavonoids, including 30 mg of genistein, 16 mg of biochanin A (a genistein precursor), 1 mg of daidzein, and 8 mg of formononetin (a daidzein precursor), or one placebo tablet, was taken daily with the evening meal. Significant increases in urinary excretion of genistein (5.22 mg/day, 95% CI: 3.72, 6.72) and daidzein (2.53 mg/day, 95% CI: 1.66, 3.40) were observed in the group taking the isoflavonoid supplement. There were no significant changes in isoflavonoid excretion in the placebo group. Clinic BP was measured at two visits, and ambulatory BP monitoring was performed over one 24-h period, at baseline and postintervention. There was no significant difference between groups, after adjustment for baseline values, in postintervention clinic supine BP (systolic 1.2 mm Hg, 95% CI: -2.3, 4.7 diastolic 0.6 mm Hg, 95% CI: -1.9, 2.5), clinic erect BP (systolic 1.7 mm Hg, 95% CI: -4.0, 8.4 diastolic 0.4 mm Hg, 95% CI: -2.4, 3.2), or 24-h ambulatory BP (systolic -1.4 mm Hg, 95% CI: -4.4, 1.6 diastolic -0.8 mm Hg, 95% CI: -2.3, 0.7). Adjustment for age, gender, and weight change did not alter the result. Therefore, these results do not support the hypothesis that isoflavonoids, and genistein in particular, are major contributors to the BP lowering effect of vegetarian diets.

Flavonoid-Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomized Controlled Clinical Trial

Publisher: Wiley

Date: 19-12-2018

DOI: 10.1002/MNFR.201700674

Abstract: The cardioprotective effects of apples are primarily attributed to flavonoids, found predominantly in the skin. This study aimed to determine if acute and/or chronic (4 weeks) ingestion of flavonoid-rich apples improves endothelial function, blood pressure (BP), and arterial stiffness in in iduals at risk for cardiovascular diseases (CVD). In this randomized, controlled cross-over trial, acute and 4 week intake of apple with skin (high flavonoid apple, HFA) is compared to intake of apple flesh only (low flavonoid apple, LFA) in 30 participants. The primary outcome is endothelial function assessed using flow-mediated dilation (FMD) of the brachial artery, while main secondary outcomes are 24 h ambulatory BP and arterial stiffness. Other outcomes include fasting serum glucose and lipoprotein profile, plasma heme oxygenase-1 (Hmox-1), F A lower risk of CVD with higher apple consumption could be mediated by the beneficial effect of apple skin on endothelial function, both acutely and chronically.

Structural requirements of flavonoids to induce heme oxygenase-1 expression

Publisher: Elsevier BV

Date: 12-2017

DOI: 10.1016/J.FREERADBIOMED.2017.09.030

Abstract: Population studies suggest cardiovascular health benefits of consuming fruits and vegetables rich in polyphenolic compounds such as flavonoids. We reported previously that the flavonoid quercetin protects arteries from oxidant-induced endothelial dysfunction and attenuates atherosclerosis in apolipoprotein E gene knockout mice, with induction of heme oxygenase-1 (Hmox1) playing a critical role. The present study investigated the structural requirements of flavonoids to induce Hmox1 in human aortic endothelial cells (HAEC). We identified ortho-dihydroxyl groups and an α,β-unsaturated system attached to a catechol as the key structural requirements for Hmox1 induction. Active but not inactive flavonoids had a low oxidation potential and prevented ascorbate autoxidation, suggesting that Hmox1 inducers readily undergo oxidation and that oxidized, rather than reduced, flavonoids may be the biological inducer of Hmox1. To test this hypothesis, we synthesized stable derivatives of caffeic acid (3-(3,4-dihyroxyphenyl)-2-propenoic acid) containing either ortho-dihydroxy or ortho-dioxo groups. Compared with the dihydroxy compound, the quinone analog induced Hmox1 more potently in HAEC and also provided enhanced protection to arteries of wild type animals against oxidant-induced endothelial dysfunction. In contrast, the quinone analog failed to provide protection against oxidant-induced endothelial dysfunction in arteries of Hmox1

Association of Vegetable Nitrate Intake With Carotid Atherosclerosis and Ischemic Cerebrovascular Disease in Older Women

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2017

DOI: 10.1161/STROKEAHA.117.016844

Abstract: A short-term increase in dietary nitrate (NO 3 − ) improves markers of vascular health via formation of nitric oxide and other bioactive nitrogen oxides. Whether this translates into long-term vascular disease risk reduction has yet to be examined. We investigated the association of vegetable-derived nitrate intake with common carotid artery intima-media thickness (CCA-IMT), plaque severity, and ischemic cerebrovascular disease events in elderly women (n=1226). Vegetable nitrate intake, lifestyle factors, and cardiovascular disease risk factors were determined at baseline (1998). CCA-IMT and plaque severity were measured using B-mode carotid ultrasound (2001). Complete ischemic cerebrovascular disease hospitalizations or deaths (events) over 14.5 years (15 032 person-years of follow-up) were obtained from the West Australian Data Linkage System. Higher vegetable nitrate intake was associated with a lower maximum CCA-IMT (B=−0.015, P =0.002) and lower mean CCA-IMT (B=−0.012, P =0.006). This relationship remained significant after adjustment for lifestyle and cardiovascular risk factors ( P ≤0.01). Vegetable nitrate intake was not a predictor of plaque severity. In total 186 (15%) women experienced an ischemic cerebrovascular disease event. For every 1 SD (29 mg/d) higher intake of vegetable nitrate, there was an associated 17% lower risk of 14.5-year ischemic cerebrovascular disease events in both unadjusted and fully adjusted models ( P =0.02). Independent of other risk factors, higher vegetable nitrate was associated with a lower CCA-IMT and a lower risk of an ischemic cerebrovascular disease event.

Vegetable-derived bioactive nitrate and cardiovascular health

Publisher: Elsevier BV

Date: 06-2017

DOI: 10.1016/J.MAM.2017.08.001

Abstract: Vegetable derived nitrate is now recognised as an important bioactive phytochemical with cardioprotective properties. Nitrate, through the recently described enterosalivary nitrate-nitrite-nitric oxide (NO) pathway, increases NO, a molecule pivotal for cardiovascular health. Clinical trials have observed that dietary nitrate has similar effects to NO when supplied exogenously. These effects include reduced blood pressure and improvements in other markers of vascular health such as endothelial function, arterial stiffness, ischemia reperfusion injury, blood flow, and platelet aggregation. Few observational studies, however, have examined dietary nitrate intake and long term cardiovascular health outcomes. This represents a significant gap in the literature. There is also a lingering concern about a possible carcinogenic effect of nitrate intake. Additionally, a number of potential factors that could impact nitrate to nitrite to NO reduction have been identified. This review will provide an overview of the evidence to date that nitrate, through its effects on endogenous NO and vascular health, is an important bioactive cardioprotective component of a diet rich in vegetables.

Plasma lipids and plasma and urinary acetyl hydrolase activity in normal and hypertensive pregnancies

Publisher: Informa UK Limited

Date: 1996

DOI: 10.3109/10641959609015690

Cytochrome P450 metabolites of arachidonic acid may be important mediators in angiotensin II-induced vasoconstriction in the rat mesentery in vivo

Publisher: Portland Press Ltd.

Date: 03-2000

DOI: 10.1042/CS19990217

Flavonoid intakes inversely associate with COPD in smokers

Publisher: European Respiratory Society (ERS)

Date: 20-01-2022

DOI: 10.1183/13993003.02604-2021

Abstract: Higher flavonoid intakes are beneficially associated with pulmonary function parameters however, their association with chronic obstructive pulmonary disease (COPD) is unknown. This study aimed to examine associations between intakes of 1) total flavonoids, 2) flavonoid subclasses and 3) major flavonoid compounds with incident COPD in participants from the Danish Diet, Cancer and Health study. This prospective cohort included 55 413 men and women without COPD, aged 50–65 years at recruitment. Habitual flavonoid intakes at baseline were estimated from a food frequency questionnaire using Phenol-Explorer. Danish nationwide registers were used to identify incident cases of COPD. Associations were modelled using restricted cubic splines within Cox proportional hazards models. During 23 years of follow-up, 5557 participants were diagnosed with COPD. Of these, 4013 were current smokers, 1062 were former smokers and 482 were never-smokers. After multivariable adjustments, participants with the highest total flavonoid intakes had a 20% lower risk of COPD than those with the lowest intakes (quintile 5 versus quintile 1: HR 0.80, 95% CI 0.74–0.87) a 6–22% lower risk was observed for each flavonoid subclass. The inverse association between total flavonoid intake and COPD was present in both men and women but only in current smokers (HR 0.77, 95% CI 0.70–0.84) and former smokers (HR 0.82, 95% CI 0.69–0.97), not never-smokers. Furthermore, higher flavonoid intakes appeared to lessen, but not negate, the higher risk of COPD associated with smoking intensity. Dietary flavonoids may be important for partially mitigating the risk of smoking-related COPD. However, smoking cessation should remain the highest priority.

Minimizing artifactual elevation of lipid peroxidation products (F 2-isoprostanes) in plasma during collection and storage

Publisher: Elsevier BV

Date: 03-2013

DOI: 10.1016/J.AB.2013.12.030

Abstract: F2-isoprostanes (F2-IsoP's) are reliable measures of in vivo lipid oxidation, but care is required to prevent artifactual elevation. We examined the effects of blood collection and storage on plasma F2-IsoP's. Blood was collected into EDTA/butylated hydroxytoluene/reduced glutathione (EDTA/BHT/GSH) or EDTA, at 4 °C or room temperature. Plasma was stored at -20 or -80 °C for 1 or 6 months before F2-IsoP's were assayed by GC-MS. The temperature of blood collection did not affect F2-IsoP's. However, storage at -20 °C or collection into EDTA resulted in significant increases in F2-IsoP's. Blood collection into EDTA/BHT/GSH and storage at -80 °C minimizes artifactual elevation of plasma F2-IsoP's.

Clinical and biochemical features, molecular diagnosis and long-term management of a case of cerebrotendinous xanthomatosis

Publisher: Elsevier BV

Date: 04-2001

DOI: 10.1016/S0009-8981(01)00391-6

Abstract: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive sterol storage disease characterised clinically by juvenile bilateral cataracts, progressive neurological dysfunction, and formation of tendon xanthomata. We describe the clinical and biochemical features, molecular diagnosis and long-term management of the first reported Australasian case of CTX. Molecular analysis confirmed the diagnosis of CTX and demonstrated that the patient was homozygous for a G-->A transition in the splice donor site of intron 4 of the sterol 27-hydroxylase gene. Serum cholestanol concentrations were decreased with the HMG-CoA reductase inhibitor simvastatin alone and greater reductions were achieved after the addition of the bile acid chenodeoxycholic acid suggesting a synergistic effect of this combination. Despite serum cholestanol concentrations remaining within the low-normal range, there has been no significant improvement in mental and physical abilities or in EEG abnormalities with 5 years of treatment. Metabolism of radiolabeled 7-ketocholesterol to aqueous soluble products was absent in CTX-derived macrophages. Consistent with this finding, plasma 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol, and 7-ketocholesterol concentrations were increased in the CTX subject compared with controls.

Differential modulation of cell cycle, apoptosis and PPARγ2 gene expression by PPARγ agonists ciglitazone and 9-hydroxyoctadecadienoic acid in monocytic cells

Publisher: Elsevier BV

Date: 05-2006

DOI: 10.1016/J.PLEFA.2006.03.002

Abstract: We sought to compare the effects of the thiazolidinedione ciglitazone with the endogenous fatty acid PPARgamma agonists 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), in U937 monocytic cells. Ciglitazone and 9-HODE inhibited cell proliferation and all three agonists increased cellular content of C18:0 fatty acids. Ciglitazone and 13-HODE resulted in an increased percentage of cells in S phase and ciglitazone reduced the percentage of cells in G2/M phase of cell cycle, whilst 9-HODE increased the percentage of cells in G0/1 and reduced the fraction in S and G2/M phases. 9-HODE selectively induced apoptosis in U937 cells, and increased PPARgamma2 gene expression. Induction of apoptosis by 9-HODE was not abrogated by the presence of the PPARgamma antagonist GW9662. Synthetic (TZD) and endogenous fatty acid ligands for PPARgamma, ciglitazone and 9- and 13-HODE, possess differential, ligand specific actions in monocytic cells to regulate cell cycle progression, apoptosis and PPARgamma2 gene expression.

HDL is the major lipoprotein carrier of plasma F2-isoprostanes

Publisher: Elsevier BV

Date: 04-2009

DOI: 10.1194/JLR.M800607-JLR200

Determinants of the Kinetics of Very Low-Density Lipoprotein Apolipoprotein B-100 in Non-Obese Men.

Publisher: Wiley

Date: 08-1997

DOI: 10.1111/J.1440-1681.1997.TB02090.X

Abstract: 1. Apolipoprotein B-100 (ApoB) is the principal structural and functional protein of the pro-atherogenic lipoproteins. Elevated plasma apoB is an independent risk factor for coronary artery disease. In the present study we aimed to assess the factors that determine the kinetics of apoB in the very low-density lipoprotein (VLDL) in healthy men. 2. We studied 17 non-obese men who were consuming an ad libitum diet and had the following characteristics: mean (+/-SD) age 45.5 +/- 9.7 years, body mass index (BMI) 25.1 +/- 1.4 kg/m2, waist:hip ratio 0.91 +/- 0.04, serum cholesterol 5.2 +/- 0.6 mmol/L, triglycerides 1.08 +/- 0.53 mmol/L and high-density lipoprotein-cholesterol 1.24 +/- 0.31 mmol/L. Daily dietary intake was as follows: total fat 76 +/- 26 g, carbohydrate 238 +/- 67 g, protein 103 +/- 33 g and alcohol 20 +/- 16 g. 3. The kinetics of VLDL ApoB were studied using a primed, constant infusion (1 mg/kg per h) of 1-[13C]-leucine over 8 h with measurement of isotopic enrichment of ApoB using gas chromatography/mass spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a monoexponential function. The mean (+/-SD) absolute hepatic secretion rate (ASR) of ApoB was 8.5 +/- 4.6 mg/kg per day and the fractional catabolic rate (FCR) was 7.9 +/- 5.6 pools/day. The ASR was significantly correlated with the waist:hip ratio (r = 0.60 P = 0.04), but not with age, BMI, weight or nutrient intake. The FCR was significantly and inversely correlated with plasma triglycerides (r = -0.53 P = 0.03) and alcohol intake (r = -0.48 P = 0.05). 4. In conclusion, the hepatic secretion of VLDL ApoB in nonobese, healthy men is primarily determined by the waist:hip ratio, a measure of visceral fat. This is consistent with the hypothesis that the rate of lipid substrate supply in the liver regulates the output of ApoB. The fractional catabolism of VLDL ApoB may, however, be inversely related to alcohol intake and appears to determine the plasma concentration of triglycerides.

20-HETE and F2-isoprostanes in the metabolic syndrome: the effect of weight reduction

Publisher: Elsevier BV

Date: 2009

DOI: 10.1016/J.FREERADBIOMED.2008.10.028

Abstract: 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 metabolite of arachidonic acid that regulates vascular function and sodium homeostasis. Studies showing an association between 20-HETE excretion, raised BMI, and oxidative stress suggest that 20-HETE may be important in the development of cardiovascular disease in the metabolic syndrome (MetS). We investigated whether 20-HETE and F(2)-isoprostanes (markers of oxidative stress) were altered in the MetS before and after weight reduction. A case-controlled comparison of 30 participants with the MetS and matched controls showed that plasma and urinary 20-HETE and F(2)-isoprostanes were significantly elevated in the MetS group. There was a significant gender x group interaction such that women with the MetS had higher urinary 20-HETE and F(2)-isoprostanes compared to controls (p<0.0001). In a randomized controlled trial, 42 participants with the MetS were assigned to 16 weeks of weight maintenance or a 12-week weight-loss program followed by 4 weeks weight stabilization. Relative to the weight-maintenance group, a 4-kg loss in weight resulted in a 2-mm Hg fall in blood pressure (BP) but did not alter urinary or plasma 20-HETE or F(2)-isoprostanes. 20-HETE and oxidative stress may be important mediators of cardiovascular disease risk in the MetS. Although a 4% reduction in body weight reduced BP, there were no changes in plasma or urinary 20-HETE or F(2)-isoprostanes.

Relationships Among Cognitive Function and Cerebral Blood Flow, Oxidative Stress, and Inflammation in Older Heart Failure Patients

Publisher: Elsevier BV

Date: 07-2016

DOI: 10.1016/J.CARDFAIL.2016.03.006

Abstract: The mechanisms for cognitive impairment in heart failure (HF) are unclear. We investigated the relative contributions of cerebral blood flow velocity (BFV), oxidative stress, and inflammation to HF-associated cognitive impairment. Thirty-six HF patients (≥60 years) and 40 healthy controls (68 ± 7 vs 67 ± 5 years, P > .05 69% vs 50% male, P > .05) completed the Cognitive Drug Research computerized assessment battery and Stroop tasks. Common carotid (CCA) and middle cerebral arterial BFV were obtained by transcranial Doppler. Blood s les were collected for oxidant (diacron-reactive oxygen metabolites F2-isoprostanes), antioxidant (coenzyme Q10 CoQ10), and inflammatory markers (high-sensitivity C-reactive protein). Compared with controls, patients exhibited impaired attention (Cognitive Drug Research's Power of Attention domain, congruent Stroop) and executive function (incongruent Stroop). Multiple regression modeling showed that CCA-BFV and CoQ10 but not group predicted performance on attention and executive function. Additionally, in HF patients, CCA-BFV and CoQ10 (β = -0.34 vs β = -0.35) were significant predictors of attention, and CCA-BFV (β = -0.34) was a predictor of executive function. Power of Attention and executive function is impaired in older HF patients, and reduced CCA-BFV and CoQ10 are associated with worse cognition. Interventions addressing these mechanisms may improve cognition in older HF patients.

P3783A higher habitual flavonoid intake is associated with a lower risk of atrial fibrillation

Publisher: Oxford University Press (OUP)

Date: 10-2019

DOI: 10.1093/EURHEARTJ/EHZ745.0632

Abstract: Our understanding of how diet affects future risk of atrial fibrillation (AF) is limited. Evidence suggests that higher habitual intakes of flavonoids, bio-active compounds found in plant-based foods and beverages, lower cardiovascular disease risk, attenuate inflammation, and may have anti-arrhythmic properties. To investigate the association between flavonoid intake and clinically apparent AF in a large cohort of Danish men and women. Baseline data from 55 634 participants without AF of the Danish Diet, Cancer and Health Study, recruited from 1993 to 1997, were cross-linked with Danish nationwide registries. Flavonoid intake was calculated from validated food frequency questionnaires using the Phenol-Explorer database. Associations between flavonoid intake and AF hospitalisation were examined using restricted cubic splines based on Cox proportional hazards models with adjustments for age, sex, BMI, smoking status, physical activity, alcohol intake, income, and hyperthyroidism. After a median [IQR] follow-up of 21 [18–22] years, 6 301 participants were hospitalised with AF. Non-linear associations were observed for total flavonoid intake and for all flavonoid sub-classes. For total flavonoid intake, after adjusting for potential lifestyle confounders and compared to participants in quintile 1 (median intake: 173 mg/day), those in quintile 3 (median intake: 320 mg/day) and quintile 4 (median intake: 494 mg/day) had a significantly lower risk of AF, with hazard ratios (95% CI) of 0.93 (0.87, 0.99) and 0.92 (0.86, 0.98), respectively. Compared to median intake in the lowest quintile, a total flavonoid intake of 1000 mg/day was associated with a lower risk of AF in smokers [0.86 (0.77, 0.96)] but not in non-smokers [0.96 (0.88, 1.05)], a lower risk of AF in high alcohol consumers [ g/d: 0.84 (0.75, 0.94)] but not in low-to-moderate alcohol consumers [ g/d: 0.97 (0.89, 1.06], a trending lower risk of AF in diabetics [0.76 (0.51, 1.14)] but not in non-diabetics [0.95 (0.89, 1.02)], and a trending lower risk of AF in those with ischaemic heart disease [0.84 (0.65, 1.09)] but not in those without [0.96 (0.89, 1.03), Figure 1]. Figure 1 We observed an inverse association between total flavonoid intake and AF, most notably in sub-populations with known lifestyle and disease risk factors for AF. This finding warrants investigation in randomised controlled trials. If confirmed, ensuring the adequate consumption of flavonoid-rich foods, particularly in in iduals “at risk”, may be an important strategy to mitigate AF risk. The Danish Diet, Cancer, and Health Study was funded by the Danish Cancer Society.

Fatty acid oxidation products in human atherosclerotic plaque: an analysis of clinical and histopathological correlates

Publisher: Elsevier BV

Date: 03-2003

DOI: 10.1016/S0021-9150(02)00391-X

Abstract: Markers of lipid peroxidative damage have been shown to be elevated in in iduals with risk factors for cardiovascular disease, and human atherosclerotic plaque contains products resulting from lipid peroxidation. In particular, the presence of fatty acid oxidation products such as hydroxyeicosatetraenoic acids (HETEs) has previously been suggested as a marker of plaque instability and symptomatic cerebrovascular disease. The aim of the present study was to quantitate the levels of various oxidation products of linoleic acid (HODEs) and arachidonic acid (HETEs), respectively, in human atherosclerotic plaque tissue and assess their level in relation to plaque histopathology, symptoms of cerebrovascular disease and preexisting atherosclerotic risk factors. We also assessed the correlation between the levels of the hydroxy fatty acid compounds and F(2)-isoprostanes, an established marker of in vivo free radical mediated oxidation. Hydroxy fatty acid oxidation products were identified in all histological subtypes of advanced plaque. However, there were no significant differences in levels between the histopathologically classified sub-groups or between patients symptomatic or asymptomatic for cerebrovascular disease. Arachidonic acid oxidation products were significantly higher in those subjects who also had symptomatic peripheral vascular disease. The level of linoleic acid oxidation products was significantly higher in in iduals who consumed alcohol on a regular basis. While F(2)-isoprostanes and fatty acid oxidation products were highly correlated (P<0.01), levels of the hydroxy fatty acid compounds were 20-40-fold higher than F(2)-isoprostanes. Chiral analysis of the plaque extracts indicated that all HODEs and HETEs originated primarily from non-enzymatic lipid peroxidation. While our results do not support previous reports that fatty acid oxidation products such as the HETEs are associated with plaque instability and symptomatic cerebrovascular disease, further work is warranted to determine the potential of these compounds as circulating markers for underlying atherosclerotic disease and lipid peroxidative stress.

Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 17-08-2021

DOI: 10.1161/JAHA.120.020551

Abstract: Dietary vitamin K (K 1 and K 2 ) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food‐frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K 1 and vitamin K 2 were estimated from the food‐frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52–60) years, 8726 in iduals were hospitalized for any ASCVD during 21 (17–22) years of follow‐up. Compared with participants with the lowest vitamin K 1 intakes, participants with the highest intakes had a 21% lower risk of an ASCVD‐related hospitalization (hazard ratio, 0.79 95% CI: 0.74–0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K 2 , the risk of an ASCVD‐related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K 2 intake (hazard ratio, 0.86 95% CI, 0.81–0.91). Risk of ASCVD was inversely associated with diets high in vitamin K 1 or K 2 . The similar inverse associations with both vitamin K 1 and K 2 , despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.

Attenuation of oxidative stress in Type 1 diabetic rats supplemented with a seasoning obtained from winemaking by-products and its effect on endothelial function

Publisher: Royal Society of Chemistry (RSC)

Date: 2016

DOI: 10.1039/C6FO01071G

Abstract: A new red wine pomace seasoning (RWPS) induced remarkable anti-hyperglycemic effects and amelioration of vascular oxidative stress in Type 1 diabetic (DB) rats.

Fish oil and multivitamin supplementation reduces oxidative stress but not inflammation in healthy older adults: A randomised controlled trial

Publisher: Elsevier BV

Date: 12-2015

DOI: 10.1016/J.JFF.2014.10.028

Effect of adding milk to black tea on vascular function in healthy men and women: a randomised controlled crossover trial

Publisher: Royal Society of Chemistry (RSC)

Date: 2018

DOI: 10.1039/C8FO01019F

Abstract: Addition of milk to black tea alters the acute/short-term benefical effect of regular black tea consumption on vascular function and blood pressure.

N-acetylcysteine prevents but does not reverse dexamethasone-induced hypertension

Publisher: Wiley

Date: 08-07-2008

DOI: 10.1111/J.1440-1681.2008.04947.X

Abstract: 1. We have shown previously that N-acetylcysteine (NAC) prevents the increase in blood pressure induced by adrenocorticotropin treatment. The present study investigated the effect of NAC on dexamethasone (Dex)-induced hypertension. 2. Male Sprague-Dawley rats were randomly ided into six groups (n = 10 in each). In a prevention study, NAC (10 g/L in the drinking water) was given for 4 days prior to and 11 days during concurrent treatment with saline (0.1 mL/rat per day) or with Dex (10 mg/rat per day). In a reversal study, daily injections of Dex or saline began 8 days before NAC and cotreatment continued for 5 days. Systolic blood pressure (SBP) was measured on alternate days using a tail-cuff system. 3. Dexamethasone significantly increased SBP from 113 +/- 4 to 139 +/- 6 mmHg (n = 10 P < 0.01). N-Acetylcysteine alone had no effect on SBP. In NAC + Dex-treated rats, SBP was significantly lower than that of Dex-treated rats (P cent < 0.01). In fully established Dex-hypertension NAC was ineffective and SBP remained high. 4. Both Dex and NAC treatments decreased bodyweight gain. N-Acetylcysteine reduced food and water consumption. Dexamethasone reduced thymus weight (P cent < 0.01) but NAC treatment did not alter this marker of glucocorticoid activity. 5. Dexamethasone tended to decrease plasma NO(x), whereas NAC restored plasma NO(x) concentrations to control levels. N-Acetylcysteine had no effect on Dex-induced increased plasma F(2)-isoprostane concentrations. 6. In conclusion, NAC partially prevented, but did not reverse, Dex-induced hypertension.

A reduction in alcohol consumption is associated with reduced plasma F2-isoprostanes and urinary 20-HETE excretion in men

Publisher: Elsevier BV

Date: 06-2007

DOI: 10.1016/J.FREERADBIOMED.2007.03.004

Abstract: There is considerable evidence that chronic moderate-to-high alcohol consumption increases blood pressure. The mechanisms by which this occurs are not clear. Alcohol consumption can induce oxidative stress and cytochrome P450 (CYP450) isoforms that are associated with oxidative stress and may influence vascular tone. To study the role of such mechanisms we examined whether reducing alcohol intake in moderate-to-heavy drinkers (40-110 g/day) resulted in changes in urinary excretion of 20-HETE, a CYP450 metabolite of arachidonic acid, and plasma and urinary F(2)-isoprostanes as markers of lipid peroxidation. After a 4-week run-in period during which healthy men maintained their usual drinking pattern they were randomized to a two-way crossover intervention study. In each of the 4-week treatment periods subjects either substituted their usual alcohol intake with a 0.9% alcohol beer or maintained their usual alcohol intake. Plasma and urinary F(2)-isoprostanes and urinary 20-HETE were measured by gas chromatography mass spectrometry, and serum gamma-glutamyl transpeptidase (gamma-GT) was measured as a biomarker of alcohol consumption, at the end of each study period. Sixteen healthy men age 51.0+/-2.7 years and with a BMI of 26.4+/-0.61 kg/m(2) completed the study. The reductions in alcohol intake (72.4+/-5.0 vs 7.9+/-1.6 g/day, p<0.001) and serum gamma-GT (geometric mean 24.4 U/L (95% CI 19.7, 30.2) vs 18.6 U/L (95% CI 15.5, 22.2, p<0.01) were accompanied by a significant fall in blood pressure as well as urinary 20-HETE excretion (158+/-23 vs 109+/-19 pmol/mmol creatinine, p<0.001) and plasma F(2)-isoprostanes (3438+/-158 vs 2929+/-145 pmol/L, p=0.01). A substantial reduction in alcohol consumption in healthy men lowered plasma F(2)-isoprostanes and urinary 20-HETE. Increased oxidative stress and 20-HETE production may be linked, at least in part, to the pathogenesis of alcohol-related hypertension.

Identification and quantitation of unique fatty acid oxidation products in human atherosclerotic plaque using high-performance liquid chromatography

Publisher: Elsevier BV

Date: 05-2001

DOI: 10.1006/ABIO.2001.5075

Dietary flavonoids and nitrate: Effects on nitric oxide and vascular function

Publisher: Oxford University Press (OUP)

Date: 24-03-2015

DOI: 10.1093/NUTRIT/NUU014

Abstract: Emerging evidence highlights dietary flavonoids and nitrate as candidates that may explain at least part of the cardioprotective effect of a fruit and vegetable diet. Nitric oxide plays a pivotal role in cardiovascular health. Components of a fruit and vegetable diet that are cardioprotective, in part through effects on nitric oxide status, could substantially reduce the cardiovascular risk profile of the general population with increased intake of such a diet. Epidemiological evidence suggests that dietary flavonoids and nitrate have a cardioprotective effect. Clinical trials with flavonoid- and nitrate-rich foods have shown benefits on measures of vascular health. While the molecular mechanisms by which flavonoids and nitrate are cardioprotective are not completely understood, recent evidence suggests both nonspecific and specific effects through nitric oxide pathways. This review presents an overview of nitric oxide and its key role in cardiovascular health and discusses the possible vascular benefits of flavonoids and nitrate, in idually and in combination, through effects on nitric oxide status.

Antioxidant activity of prenylated flavonoids from the West African medicinal plant Dorstenia mannii

Publisher: Elsevier BV

Date: 07-2003

DOI: 10.1016/S0378-8741(03)00108-9

Abstract: The antioxidant activities of three prenylated flavonoids from Dorstenia mannii (6,8-diprenyleriodictyol, dorsmanin C and dorsmanin F) were compared to the common, non-prenylated flavonoid, quercetin. The prenylated flavonoids were found to be potent scavengers of the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), and are more potent than butylated hydroxy toluene (BHT), a common antioxidant used as a food additive. The prenylated flavonoids also inhibited Cu(2+)-mediated oxidation of human low density lipoprotein (LDL). Dose-response studies indicated that the prenylated flavonoids were effective inhibitors of lipoprotein oxidation with IC50 values <1 microM and had similar inhibitory potency compared to quercetin, but was not directly related to Cu binding. Unlike quercetin, they did not show any pro-oxidant activity at high doses in the Cu(2+)-mediated lipoprotein oxidation system. The medicinal action of Dorstenia mannii may be related to the high concentration of potent antioxidant prenylated flavonoids in this species.

Differential regulation of endobiotic-oxidizing cytochromes P450 in vitamin A-deficient male rat liver

Publisher: Wiley

Date: 12-2001

DOI: 10.1038/SJ.BJP.0704380

Effects of tea and coffee on cardiovascular disease risk

Publisher: Royal Society of Chemistry (RSC)

Date: 2012

DOI: 10.1039/C2FO10288A

Abstract: Tea and coffee have been associated with risk of cardiovascular disease (CVD), both positively and negatively. Epidemiological data suggest that black and green tea may reduce the risk of both coronary heart disease and stroke by between 10 and 20%. Experimental and clinical trial data generally indicate either neutral or beneficial effects on risk factors and pathways linked to the development of CVD. Controversy still exists regarding the effects of coffee, where there have been concerns regarding associations with hypercholesterolaemia, hypertension and myocardial infarction. However, long term moderate intake of coffee is not associated with detrimental effects in healthy in iduals and may even protect against the risk of developing type 2 diabetes. The detrimental effects of coffee may be associated with the acute pressor effects, most likely due to caffeine at high daily intakes, and lipids from boiled coffee can contribute to raised serum cholesterol. Genetic polymorphisms in enzymes involved in uptake, metabolism and excretion of tea and coffee compounds are also associated with differential biological effects. Potential mechanisms by which tea and coffee phytochemicals can exert effects for CVD protection include the regulation of vascular tone through effects on endothelial function, improved glucose metabolism, increased reverse cholesterol transport and inhibition of foam cell formation, inhibition of oxidative stress, immunomodulation and effects on platelet function (adhesion and activation, aggregation and clotting). The phytochemical compounds in tea and coffee and their metabolites are suggested to influence protective endogenous pathways by modulation of gene-expression. It is not known exactly which compounds are responsible for the suggestive protective effects of tea and coffee. Although many biologically active compounds have been identified with known biological effects, tea and coffee contain many unidentified compounds with potential bioactivity.

F2-Isoprostanes in HDL are bound to neutral lipids and phospholipids

Publisher: Informa UK Limited

Date: 07-11-2016

DOI: 10.1080/10715762.2016.1250262

Abstract: Low HDL cholesterol (HDL-C) is a risk factor for coronary artery disease (CAD). However, interventions that raise HDL-C have failed to reduce cardiovascular events. We previously reported that HDL is the main carrier of plasma F

Glutathionyl haemoglobin is not increased in diabetes nor related to glycaemia, complications, dyslipidaemia, inflammation or other measures of oxidative stress

Publisher: Elsevier BV

Date: 05-2008

DOI: 10.1016/J.DIABRES.2008.01.012

Nitration of γ-tocopherol prevents its oxidative metabolism by HepG2 cells

Publisher: Elsevier BV

Date: 08-2005

DOI: 10.1016/J.FREERADBIOMED.2005.04.001

Abstract: Gamma-tocopherol (gammaT) is one of the major forms of vitamin E consumed in the diet. Previous reports have suggested increased levels of nitrated gamma-tocopherol (5-NO2-gammaT) in smokers and in iduals with conditions associated with elevated nitrative stress. The monitoring of 5-NO2-gammaT and its possible metabolite(s) may be a useful marker of reactive nitrogen species generation in vivo. The major pathway for the metabolism of gammaT is the cytochrome P450 dependent oxidation to its water-soluble metabolite gamma-CEHC, which is excreted in urine. In order to determine if 5-NO2-gammaT could be metabolised via the same route and detected in urine we developed a sensitive gas chromatography-mass spectrometry assay for 5-NO2-gamma-CEHC. 5-NO2-gamma-CEHC was synthesised and its structure confirmed by proton nuclear magnetic resonance and mass spectrometry. While gamma-CEHC was abundant in urine from healthy volunteers, as well as patients with coronary heart disease and type 2 diabetes, 5-NO2-gamma-CEHC was undetectable (limit of detection of 5 nM). To understand this observation we examined the uptake and metabolism of gammaT and 5-NO2-gammaT by HepG2 cells. gammaT was readily incorporated into cells and metabolised to gamma-CEHC over a period of 48 hours. In contrast, 5-NO2-gammaT was poorly incorporated into HepG2 cells and not metabolised to 5-NO2-gamma-CEHC over the same time period. We conclude that nitration of gammaT prevents its incorporation into liver cells and therefore its metabolism to the water-soluble metabolite. Whether 5-NO2-gammaT could be metabolised via other pathways in vivo requires further investigation.

Apple intake is inversely associated with all-cause and disease-specific mortality in elderly women

Publisher: Cambridge University Press (CUP)

Date: 20-01-2016

DOI: 10.1017/S0007114515005231

Abstract: Higher fruit intake is associated with lower risk of all-cause and disease-specific mortality. However, data on in idual fruits are limited, and the generalisability of these findings to the elderly remains uncertain. The objective of this study was to examine the association of apple intake with all-cause and disease-specific mortality over 15 years in a cohort of women aged over 70 years. Secondary analyses explored relationships of other fruits with mortality outcomes. Usual fruit intake was assessed in 1456 women using a FFQ. Incidence of all-cause and disease-specific mortality over 15 years was determined through the Western Australian Hospital Morbidity Data system. Cox regression was used to determine the hazard ratios (HR) for mortality. During 15 years of follow-up, 607 (41·7 %) women died from any cause. In the multivariable-adjusted analysis, the HR for all-cause mortality was 0·89 (95 % CI 0·81, 0·97) per sd (53 g/d) increase in apple intake, HR 0·80 (95 % CI 0·65, 0·98) for consumption of 5–100 g/d and HR 0·65 (95 % CI 0·48, 0·89) for consumption of g/d (an apple a day), compared with apple intake of g/d ( P for trend =0·03). Our analysis also found that higher apple intake was associated with lower risk for cancer mortality, and that higher total fruit and banana intakes were associated lower risk of CVD mortality ( P ·05). Our results support the view that regular apple consumption may contribute to lower risk of mortality.

Vitamin E Supplementation and Hepatic Drug Metabolism in Humans

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 12-2009

DOI: 10.1097/FJC.0B013E3181BFAE18

Augmentation of monocyte intracellular ascorbate in vitro protects cells from oxidative damage and inflammatory responses

Publisher: Elsevier BV

Date: 07-2006

DOI: 10.1016/J.BBRC.2006.04.174

Abstract: Ascorbic acid is present as a primary antioxidant in plasma and within cells, protecting both cytosolic and membrane components of cells from oxidative damage. The effects of intracellular ascorbic acid on F(2)-isoprostanes (biomarkers of oxidative stress) and monocyte chemoattractant protein-1 (marker of inflammatory responses) production in monocytic THP-1 cells were investigated under conditions of 2,2'-Azobis(2-methylpropionamidine)dihydrochloride (AAPH) induced oxidative stress. Cells cultured under normal conditions have extremely low ascorbate levels and the intracellular ascorbate can be augmented significantly by adding ascorbate to the culture medium. While AAPH treatment reduced cell viability, increased F(2)-isoprostanes and MCP-1 production, the presence of intracellular ascorbic acid maintained high cell viability and attenuated both F(2)-isoprostanes and MCP-1 production. Measurement of intracellular ascorbic acid and its oxidised products showed that intracellular ASC was oxidised to a significantly greater extent during AAPH treatment and may be utilised to protect the cells under conditions of oxidative stress. This study demonstrates the importance of intracellular ascorbate, which may be lacking under normal cell culture conditions, under conditions of increased oxidative stress.

Association of flavonoids and flavonoid-rich foods with all-cause mortality: The Blue Mountains Eye Study

Publisher: Elsevier BV

Date: 2020

DOI: 10.1016/J.CLNU.2019.01.004

Abstract: Higher intakes of flavonoids provide health benefits, however, the importance of each flavonoid class and which population groups may receive the greatest protection from higher flavonoid intake warrants further investigation. To explore the associations of flavonoid and flavonoid-rich wholefood intakes with all-cause mortality and the moderating effects of early mortality risk factors. The study included 2349 participants of The Blue Mountains Eye Study, with a mean ± SD age at baseline of 64.7 ± 9.2 years. Flavonoid intake was calculated from baseline food frequency questionnaires using US Department of Agriculture food composition databases. Associations were examined using adjusted Cox proportional hazards models. After 14 years of follow-up, 677 participants died. There was a flavonoid threshold effect with the greatest risk reduction seen between low and moderate intakes of total flavonoids, flavonoid classes and flavonoid-rich foods. Amongst the whole cohort, participants in the highest tertile of anthocyanidin intake had a significantly lower risk of all-cause mortality [multivariable adjusted HR (95%CI): 0.76 (0.61, 0.94)] when compared to those in the lowest tertile. Amongst participants with at least one early mortality risk factor (smoking, high alcohol consumption, no regular exercise or obesity), risk of all-cause mortality was lower in those in the highest intake tertile for total flavonoids [adjusted HR: 0.77 (0.59, 1.00)], flavan-3-ols [0.75 (0.58, 0.98)], anthocyanidins [0.70 (0.54, 0.92)], and proanthocyanidins [0.69 (0.52, 0.92)], compared to those in the lowest tertile. No similar associations were observed among those without any risk factors. Similarly, consumption of apples, tea and the in idual flavonoid compounds, quercetin and epicatechin, were associated with a lower risk of all-cause mortality among participants with at least one risk factor, but not amongst other participants. Moderate to high intakes of flavonoids and certain flavonoid subclasses may provide health benefits, particularly for in iduals with at least one early mortality risk factor.

Performance of Urinary Phenyl-γ-Valerolactones as Biomarkers of Dietary Flavan-3-ol Exposure

Publisher: Elsevier BV

Date: 08-2023

DOI: 10.1016/J.TJNUT.2023.06.035

Nitrate, the oral microbiome, and cardiovascular health: a systematic literature review of human and animal studies

Publisher: Elsevier BV

Date: 04-2018

DOI: 10.1093/AJCN/NQX046

Abstract: Dietary nitrate is an important source of nitric oxide (NO), a molecule critical for cardiovascular health. Nitrate is sequentially reduced to NO through an enterosalivary nitrate-nitrite-NO pathway that involves the oral microbiome. This pathway is considered an important adjunct pathway to the classical l-arginine-NO synthase pathway. The objective of this study was to systematically assess the evidence for dietary nitrate intake and improved cardiovascular health from both human and animal studies. A systematic literature search was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by using key search terms in Medline and EMBASE databases and defined inclusion and exclusion criteria. Thirty-seven articles on humans and 14 articles on animals were included from 12,541 screened references. Data on the effects of dietary nitrate on blood pressure, endothelial function, ischemic reperfusion injury, arterial stiffness, platelet function, and cerebral blood flow in both human and animal models were identified. Beneficial effects of nitrate on vascular health have predominantly been observed in healthy human populations, whereas effects in populations at risk of cardiovascular disease are less clear. Few studies have investigated the long-term effects of dietary nitrate on cardiovascular disease clinical endpoints. In animal studies, there is evidence that nitrate improves blood pressure and endothelial function, particularly in animal models with reduced NO bioavailability. Nitrate dose seems to be a critical factor because there is evidence of cross-talk between the 2 pathways of NO production. Evidence for a beneficial effect in humans at risk of cardiovascular disease is limited. Furthermore, there is a need to investigate the long-term effects of dietary nitrate on cardiovascular disease clinical endpoints. Further animal studies are required to elucidate the mechanisms behind the observed effects.

Effects of black tea on body composition and metabolic outcomes related to cardiovascular disease risk: a randomized controlled trial

Publisher: Royal Society of Chemistry (RSC)

Date: 2014

DOI: 10.1039/C4FO00209A

Abstract: This randomised controlled double-blind 6 month parallel-designed trial indicates that ingestion of black tea over 3 months can improve body weight and body composition.

Dietary polyphenols: Antioxidants or not?

Publisher: Elsevier BV

Date: 04-2016

DOI: 10.1016/J.ABB.2015.11.014

Abstract: Population studies have shown a strong association between dietary intake of polyphenols and reduced risk of cardiovascular disease. These associations have been confirmed to some extent by intervention studies which have shown improvements in vascular function and blood pressure with certain polyphenols or food extracts rich in polyphenols. The mechanisms involved in the bioactivity of dietary polyphenols is still under active investigation. It is unlikely that polyphenols act as antioxidants in vivo. Evidence suggests that dietary polyphenols or their metabolites act as signalling molecules and can increase nitric oxide bioavailability and induce protective enzymes. This review will outline some of the key issues in dietary polyphenol research that suggest mechanistic insights into the action of these bioactive compounds. There are a number of issues that remain to be resolved in bridging the gap between observational studies and intervention trials using food extracts or pure polyphenol compounds.

Antibacterial mouthwash blunts oral nitrate reduction and increases blood pressure in treated hypertensive men and women

Publisher: Oxford University Press (OUP)

Date: 30-10-2015

DOI: 10.1093/AJH/HPU192

Abstract: Endothelial nitric oxide (NO) is fundamental to cardiovascular health. Dietary nitrate and nitrate from endothelial derived NO metabolism provides a significant contribution to the circulating NO pool through the nitrate-nitrite-NO pathway. A critical step in this pathway is the reduction of nitrate to nitrite by the oral microbiota. We aimed to assess the effects of antibacterial mouthwash use on markers of nitrate-nitrite-NO metabolism and blood pressure in treated hypertensive men and women. Fifteen treated hypertensive men and women (mean age 65 years) were recruited to a randomized controlled cross-over trial. The effects of 3-day use of antibacterial mouthwash on oral nitrate to nitrite reduction, salivary and plasma nitrate and nitrite, plasma cyclic guanosine monophosphate (cGMP) and systolic and diastolic blood pressure were compared to control (water). Relative to control, 3-day antibacterial mouthwash use resulted in decreased oral nitrate to nitrite reduction (P = 0.02), decreased salivary nitrite (P = 0.01) and increased salivary nitrate (P < 0.001), and there was a trend toward a decrease in plasma nitrite concentration (P = 0.09). Use of antibacterial mouthwash over 3 days also resulted in higher systolic blood pressure (2.3mm Hg 95% CI: 0.5, 4.0 P = 0.01), but not diastolic blood pressure (P = 0.4) or plasma cGMP (P = 0.7), relative to control. Interruption of the nitrate-nitrite-NO pathway through the use of antibacterial mouthwash was paralleled by a small elevation of systolic blood pressure in treated hypertensive men and women.

Taurine supplementation increases skeletal muscle force production and protects muscle function during and after high-frequency in vitro stimulation

Publisher: American Physiological Society

Date: 07-2009

DOI: 10.1152/JAPPLPHYSIOL.00040.2009

Abstract: Recent studies report that depletion and repletion of muscle taurine (Tau) to endogenous levels affects skeletal muscle contractility in vitro. In this study, muscle Tau content was raised above endogenous levels by supplementing male Sprague-Dawley rats with 2.5% (wt/vol) Tau in drinking water for 2 wk, after which extensor digitorum longus (EDL) muscles were examined for in vitro contractile properties, fatigue resistance, and recovery from fatigue after two different high-frequency stimulation bouts. Tau supplementation increased muscle Tau content by ∼40% and isometric twitch force by 19%, shifted the force-frequency relationship upward and to the left, increased specific force by 4.2%, and increased muscle calsequestrin protein content by 49%. Force at the end of a 10-s (100 Hz) continuous tetanic stimulation was 6% greater than controls, while force at the end of the 3-min intermittent high-frequency stimulation bout was significantly higher than controls, with a 12% greater area under the force curve. For 1 h after the 10-s continuous stimulation, tetanic force in Tau-supplemented muscles remained relatively stable while control muscle force gradually deteriorated. After the 3-min intermittent bout, tetanic force continued to slowly recover over the next 1 h, while control muscle force again began to decline. Tau supplementation attenuated F 2 -isoprostane production (a sensitive indicator of reactive oxygen species-induced lipid peroxidation) during the 3-min intermittent stimulation bout. Finally, Tau transporter protein expression was not altered by the Tau supplementation. Our results demonstrate that raising Tau content above endogenous levels increases twitch and subtetanic and specific force in rat fast-twitch skeletal muscle. Also, we demonstrate that raising Tau protects muscle function during high-frequency in vitro stimulation and the ensuing recovery period and helps reduce oxidative stress during prolonged stimulation.

Monocyte-derived macrophages from men and women with Type 2 diabetes mellitus differ in fatty acid composition compared with non-diabetic controls

Publisher: Elsevier BV

Date: 03-2007

DOI: 10.1016/J.DIABRES.2006.07.009

Abstract: We examined whether macrophages from men and women with Type 2 diabetes mellitus (T2DM) exhibited differences in expression of key genes involved in fatty acid metabolism and in fatty acid composition compared with macrophages from non-diabetic controls. Peripheral blood monocytes from subjects with T2DM (n=9) and non-diabetic controls (n=10) were differentiated into macrophages in 10% autologous serum and normal (5mM) or high (22mM) glucose. Levels of PPARalpha, PPARgamma, LXRalpha, SCD and ABCA1 mRNAs were similar in macrophages from subjects with T2DM and controls. At 5mM glucose, macrophage stearic acid (C18:0) was 12.6+/-1.0% of total fatty acids for T2DM compared with 18.1+/-2.0% for controls (p=0.03). Macrophage linoleic acid (C18:2) was 15.5+/-0.8% for T2DM and 9.3+/-2.0% for controls (p=0.005). The ratio of macrophage stearic acid (C18:0)/oleic acid (C18:1) was 0.29 [0.25,0.48] for T2DM versus 0.54 [0.36,0.82] for controls (p=0.04). Compared with non-diabetic controls, macrophages from men and women with T2DM had significantly different fatty acid profiles consistent with increased stearoyl-CoA desaturase (SCD) activity and increased C18:2 accumulation. This pattern of altered macrophage fatty acid composition may be relevant to diabetic atherogenesis.

Effects of Chewing Gum on Nitric Oxide Metabolism, Markers of Cardiovascular Health and Neurocognitive Performance after a Nitrate-Rich Meal

Publisher: Informa UK Limited

Date: 18-02-2021

DOI: 10.1080/07315724.2020.1869119

Abstract: Cardiovascular and neurocognitive responses to chewing gum have been reported, but the mechanisms are not well understood. Chewing gum after a nitrate-rich meal may upregulate the reduction of oral nitrate to nitrite and increase nitric oxide (NO), a molecule important to cardiovascular and neurocognitive health. We aimed to explore effects of chewing gum after a nitrate-rich meal on nitrate metabolism (through the enterosalivary nitrate-nitrite-NO pathway), endothelial function, blood pressure (BP), neurocognitive performance, mood and anxiety. Twenty healthy men (n = 6) and women (n = 14) with a mean age of 48 years (range: 23-69) were recruited to a randomized controlled cross-over trial. After consumption of a nitrate-rich meal (180 mg of nitrate), we assessed the acute effects of chewing gum, compared to no gum chewing, on (i) salivary nitrate, nitrite and the nitrate reductase ratio (100 x [nitrite]/([nitrate] + [nitrite]) (ii) plasma nitrite, Consumption of the nitrate-rich meal resulted in a significant increase in markers of nitrate metabolism. A significantly higher peak flow mediated dilatation was observed with chewing compared to no chewing (baseline adjusted mean difference: 1.10%, 95% CI: 0.06, 2.14 p = 0.038) after the nitrate-rich meal. A significant small increase in systolic BP, diastolic BP and heart rate were observed with chewing compared to no chewing after the nitrate-rich meal. The study did not observe increased oral reduction of nitrate to nitrite and NO, or improvements in neurocognitive performance, mood or anxiety with chewing compared to no chewing. Chewing gum after a nitrate-rich meal resulted in an acute improvement in endothelial function and a small increase in BP but did not result in acute effects on neurocognitive function, mood or anxiety.

Habitual flavonoid intake and ischemic stroke incidence in the Danish Diet, Cancer, and Health Cohort

Publisher: Elsevier BV

Date: 07-2021

DOI: 10.1093/AJCN/NQAB138

Short-term effects of a high nitrate diet on nitrate metabolism in healthy individuals

Publisher: MDPI AG

Date: 12-03-2015

DOI: 10.3390/NU7031906

Antihypertensive and antioxidant effects of supplementation with red wine pomace in spontaneously hypertensive rats

Publisher: Royal Society of Chemistry (RSC)

Date: 2017

DOI: 10.1039/C7FO00390K

Abstract: 4-Week supplementation with a new red wine pomace seasoning (RWPS) decreased blood pressure, ameliorated vascular oxidative stress, and improved NO bioavailability in Spontaneously Hypertensive Rats (SHR).

Specialized proresolving lipid mediators in humans with the metabolic syndrome after n-3 fatty acids and aspirin

Publisher: Elsevier BV

Date: 12-2015

DOI: 10.3945/AJCN.115.116384

Abstract: The metabolic syndrome (MetS) is associated with a chronic low-grade inflammatory state and may be affected by the ability to resolve inflammation, which is an active process that involves specialized proresolving lipid mediators (SPMs) derived from n-3 (ω-3) fatty acids. We compared plasma concentrations of SPMs in men and women with features of the MetS and in healthy matched control subjects in response to intakes of n-3 fatty acids and aspirin. MetS volunteers (n = 22) and healthy, matched controls (n = 21) were studied in parallel for 4 wk. Both groups took n-3 fatty acids (2.4 g/d) for 4 wk with the addition of aspirin (300 mg/d) during the last 7 d. Blood was collected at baseline and at 3 and 4 wk. Plasma SPMs were measured with the use of liquid chromatography-tandem mass spectrometry and included 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins, 17-hydroxydocosahexaenoic acid (17-HDHA), D-series resolvins, 14-hydroxydocosahexaenoic acid (14-HDHA), and maresin-1. Baseline SPMs did not differ between groups. There was an increase in the SPM precursors 18-HEPE, 17-HDHA, and 14-HDHA after n-3 fatty acid supplementation that was significantly attenuated in the MetS (P < 0.05). However, the E-series resolvins increased to a similar extent in the groups after n-3 fatty acid supplementation, and the D-series resolvins were not different from those at baseline. The addition of aspirin to n-3 fatty acids did not alter any SPMs in either group. Volunteers with MetS had reduced plasma concentrations of the precursors of the E- and D- series resolvins as well as of 14-HDHA in response to n-3 fatty acid supplementation. However, plasma E-series resolvins were increased to a similar extent after n-3 fatty acid supplementation in both groups, and the addition of aspirin to n-3 fatty acid supplementation did not alter any of the plasma SPMs in MetS and control subjects. Additional studies in the MetS are required to determine whether SPMs affect the ability to mount an appropriate response to infection. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12610000708055.

Association between vitamin K1 intake and mortality in the Danish Diet, Cancer, and Health cohort

Publisher: Springer Science and Business Media LLC

Date: 30-09-2021

DOI: 10.1007/S10654-021-00806-9

Abstract: Reported associations between vitamin K 1 and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52–60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K 1 (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87–192 µg/d) intake of vitamin K 1 was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K 1 intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K 1 may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level.

Effect of Iron Chelation on Myocardial Infarct Size and Oxidative Stress in ST-Elevation–Myocardial Infarction

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 04-2012

DOI: 10.1161/CIRCINTERVENTIONS.111.966226

Abstract: Experimental studies suggest that deferoxamine (DFO) limits the generation of reactive oxygen species by chelating redox-active iron and thereby may reduce ischemia-reperfusion injury and myocardial infarct (MI) size. We investigated whether DFO administered before reperfusion by primary percutaneous coronary intervention (PPCI) would ameliorate oxidative stress and MI size. We randomly assigned 60 patients with ST-elevation–MI to receive an intravenous bolus of DFO (500 mg) immediately before PPCI followed by a 12-hour infusion (50 mg/kg of body weight) (n=28) or normal saline bolus and infusion (placebo group, n=32). MI size was measured by contrast-enhanced cardiac MRI (CMRI day 3±1), creatine kinase and troponin I area-under-the-curve, and severity of wall motion abnormality on echocardiography. Clinical follow-up including repeat CMRI and echocardiography were performed at 3 months (100±17 days). Oxidative stress was assessed by plasma F 2 -isoprostane levels. DFO and placebo groups were well balanced with respect to baseline characteristics, symptom- and door-to-balloon times, pre-PPCI coronary patency, and infarct-related artery location. Serum iron levels were decreased with DFO treatment after PPCI compared with placebo (3.0±2.5 versus 12.6±5.5 μmol/L, P .0001), which persisted until the end of the infusion. In DFO-treated patients, there was a significant reduction in plasma F 2 -isoprostane levels immediately after PPCI (2878±1461 versus 2213±579 pmol/L, P =0.04). However, there was no difference in CMRI-determined infarct size (DFO, 17.4±10.8%, versus placebo, 18.6±10.2% P =0.73), myocardial salvage index at 3 days or at 3 months, or the area-under-the-curve for creatine kinase or troponin I. Adjunctive DFO treatment after the onset of ischemia and continued periprocedurally ameliorates oxidative stress without limiting infarct size. URL: www.anzctr.org.au/ . Unique identifier: ACTRN12608000308392.

Fish oil (SMOFlipid) and olive oil lipid (clinoleic) in very preterm neonates

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 02-2014

DOI: 10.1097/MPG.0000000000000174

Beneficial effects of inorganic nitrate in non-alcoholic fatty liver disease

Publisher: Elsevier BV

Date: 10-2021

DOI: 10.1016/J.ABB.2021.109032

Acute effects of quercetin-3-O-glucoside on endothelial function and blood pressure: A randomized dose-response study

Publisher: Elsevier BV

Date: 07-2016

DOI: 10.3945/AJCN.116.131268

Abstract: Epidemiologic studies have suggested that a flavonoid-rich diet can reduce the risk of developing cardiovascular disease. Certain flavonoids, in particular quercetin, have been shown to ameliorate endothelial dysfunction and reduce blood pressure (BP), possibly by increasing the bioavailability of the potent vasodilator nitric oxide (NO). Several studies have indicated that improvements in measures of cardiovascular health do not occur linearly, but rather, plateau or decrease with an increasing dose of flavonoids. We determined whether the acute administration of increasing doses of a common quercetin glycoside (quercetin-3-O-glucoside) improves endothelial function and reduces BP in a dose-dependent manner. We also explored whether any effects were correlated with changes in plasma NO production. A randomized, controlled, crossover study was performed in 15 healthy volunteers who each completed 5 visits with a minimum washout period of 1 wk between testing days. Participants received each of the following 5 interventions in a random order: 1) 0, 2) 50, 3) 100, 4) 200, or 5) 400 mg quercetin-3-O-glucoside. Endothelial function and BP were assessed before and 60 min after intervention. A blood s le was taken before and 90 min after intervention for the analysis of plasma nitrate and nitrite as markers of NO production as well as of plasma quercetin metabolites. Although we observed a significant correlation between the dose of quercetin-3-O-glucoside and plasma concentrations of total quercetin (R(2) = 0.52, P < 0.001) and isorhamnetin (R(2) = 0.12, P = 0.005), we showed no improvements in endothelial function or BP and no changes in NO production after any dose. From these results, we conclude that there are no acute changes in BP or the NO-mediated endothelium-dependent relaxation of the brachial artery with doses of quercetin ranging from 50 to 400 mg in healthy men and women. This trial was registered at www.anzctr.org.au as ACTRN12615001338550.

Black tea lowers the rate of blood pressure variation: a randomized controlled trial

Publisher: Elsevier BV

Date: 05-2013

DOI: 10.3945/AJCN.112.051375

Abstract: Measures of blood pressure variation have been associated with cardiovascular disease and related outcomes. The regular consumption of black tea can lower blood pressure, but its effects on blood pressure variation have yet to be investigated. We aimed to assess the effects of black tea consumption on the rate of ambulatory blood pressure variation. Men and women (n = 111) with systolic blood pressure between 115 and 150 mm Hg at screening were recruited in a randomized, controlled, double-blind, 6-mo parallel-designed trial designed primarily to assess effects on blood pressure. Participants consumed 3 cups/d of either powdered black tea solids (tea) or a flavonoid-free caffeine-matched beverage (control). The 24-h ambulatory blood pressure level and rate of measurement-to-measurement blood pressure variation were assessed at baseline, day 1, and 3 and 6 mo. Across the 3 time points, tea, compared with the control, resulted in lower rates of systolic (P = 0.0045) and diastolic (P = 0.016) blood pressure variation by ~10% during nighttime (2200-0600). These effects, which were immediate at day 1 and sustained over 6 mo, were independent of the level of blood pressure and heart rate. The rate of blood pressure variation was not significantly altered during daytime (0800-2000). These findings indicate that a component of black tea solids, other than caffeine, can influence the rate of blood pressure variation during nighttime. Thus, small dietary changes have the potential to significantly influence the rate of blood pressure variation. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTR12607000543482.

Higher habitual dietary flavonoid intake associates with lower central blood pressure and arterial stiffness in healthy older adults

Publisher: Cambridge University Press (CUP)

Date: 23-08-2021

DOI: 10.1017/S000711452100324X

Abstract: Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 ( sd 4·1) years BMI, 26·4 ( sd 4·41) kg/m 2 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd /d higher intake of anthocyanins (( sd 44·3) mg/d) was associated with significantly lower cDBP (−1·56 mmHg, 95 % CI −2·65, −0·48) and cMAP (−1·62 mmHg, 95 % CI −2·82, −0·41). Similarly, each sd /d higher intake of flavanones (( sd 19·5) mg/d) was associated with ~1 % lower cAIx (−0·93 %, 95 % CI −1·77, −0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n -3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness these findings require corroboration in further research.

Is reversal of endothelial dysfunction by tea related to flavonoid metabolism?

Publisher: Cambridge University Press (CUP)

Date: 2006

DOI: 10.1079/BJN20051621

Abstract: Dietary flavonoids can improve endothelial function, but the response varies between in iduals. Wide variability is also seen in flavonoid O-methylation, a major pathway of flavonoid metabolism. The O-methylation of flavonoids could alter activity, and thus influence any effect on endothelial function. The objective of the current analysis was to investigate whether variability in the endothelial function response to ingestion of tea, a rich source of flavonoids, is related to the degree of O-methylation of flavonoids. This relationship was investigated in two studies in which endothelium-dependent flow-mediated dilatation (FMD) of the brachial artery was assessed and urinary 4- O -methylgallic acid (4OMGA) excretion was used as a marker of the O-methylation of tea-derived flavonoids. In the first study, amongst participants consuming five cups of tea per day for 4 weeks, the degree of increase in 4OMGA excretion was inversely associated with the change in FMD responses ( r −078, p =0·008). In the second study, there was a significant difference in the FMD responses to acute ingestion of three cups of tea between in iduals with a low ( median) and high ( median) 4OMGA response (1·94 (sem 0·79) % and −0·25 (sem 0·53) %, respectively p =0·03). That is, any improvement in FMD following ingestion of tea may be enhanced in in iduals who O-methylate less of the absorbed flavonoids. The present results are consistent with the suggestion that differences in flavonoid metabolism may influence their effect on endothelial function. Thus, differences in flavonoid metabolism could be related to the level of benefit of dietary flavonoids on the risk of CVD.

Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects

Publisher: Elsevier BV

Date: 10-2003

DOI: 10.1016/S0891-5849(03)00407-6

Abstract: n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms. Despite this, there has been concern that these fatty acids may increase lipid peroxidation. The data in vivo are inconclusive, due in part to limitations in the methodologies. In this regard, the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress. This study aimed to assess the effects of supplementation with purified eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), the two major n-3 fatty acids, on urinary F2-isoprostanes and markers of inflammation, in type 2 diabetic patients. In a double-blind, placebo controlled trial of parallel design, 59 nonsmoking, treated-hypertensive, type 2 diabetic subjects, were randomized to 4 g daily of purified EPA, DHA, or olive oil for 6 weeks, while maintaining their usual diet. F2-isoprostanes, measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), were measured before and after intervention. Thirty-nine men and 12 women aged 61.2 +/- 1.2 years, with body mass index (BMI), 29.5 +/- 0.5 kg/m2 24 h blood pressure, 138/73 mmHg HbA1c, 7.3 +/- 0.1% and fasting glucose, 7.9 +/- 0.2 mmol/l completed the intervention. Baseline urinary F2-isoprostanes were positively associated with HbA1c (p=.011) and fasting glucose (p=.032). Relative to the olive oil group, postintervention urinary F2-isoprostanes were decreased 19% by EPA (p=.017) and 20% by DHA (p=.014). There were no significant changes in CRP, IL-6, and TNF-alpha following EPA or DHA supplementation. In regression analysis, Delta F2-isoprostanes were positively associated with Delta HbA1c (p=.007) independent of treatment group and with Delta TNF-alpha (p=.034) independent of age, gender, BMI, and treatment group. There were no associations with Delta CRP or Delta IL-6. This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation, in treated hypertensive, type 2 diabetic subjects.

A Systematic Review of the Sources of Dietary Salt Around the World

Publisher: Elsevier BV

Date: 05-2020

DOI: 10.1093/ADVANCES/NMZ134

Acute effects of red wine on cytochrome P450 eicosanoids and blood pressure in men

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 11-2013

DOI: 10.1097/HJH.0B013E328364A27F

A food composition database for assessing nitrate intake from plant-based foods

Publisher: Elsevier BV

Date: 11-2022

DOI: 10.1016/J.FOODCHEM.2022.133411

Abstract: An up-to-date nitrate food composition database of plant-based foods is lacking. Such a resource is imperative to obtain a robust assessment of dietary nitrate intakes and facilitate more empirical evaluation of health implications. We updated and expanded our 2017 vegetable nitrate database by including data published between 2016 and 2021, and data on fruits, cereals, herbs, spices, pulses and nuts (1980 - 2021). Of the collated nitrate contents for 264 plant-based foods from 64 countries, 120 were obtained from three or more references. Despite substantial variations, leaf vegetables were the top nitrate-containing foods, followed by stem & shoot vegetables, herbs and spices, root vegetables, flower vegetables, tuber vegetables, nuts, fruit vegetables, legume/seed vegetables, fruits and cereals. Banana and strawberry contained far higher amounts of nitrate than previously recognised. In conjunction with the recent animal-based food nitrate & nitrite database, this database can now be used to evaluate dietary nitrate intake in clinical and epidemiological studies.

Measurement of urinary F2-isoprostanes by gas chromatography-mass spectrometry is confounded by interfering substances

Publisher: Informa UK Limited

Date: 23-11-2010

DOI: 10.3109/10715760903390838

Abstract: Analysis of F(2)-isoprostanes in urine using gas chromatography-mass spectrometry is confounded by the presence of endogenous compounds interfering with the internal standard, 15-F(2t)-IsoP-d(4) (m/z 573). Previous efforts to resolve the 15-F(2t)-IsoP-d(4) from co-eluting peaks with different solid phase extractions were unsuccessful. This study has now used a highly-deuterated, d(9)-analogue of the derivatization agent N,O-Bis(trimethyl-d(9)-silyl) trifluoroacetamide (BSTFA-d(9)) yielding trimethylsilyl ethers, but this was not successful in resolving the 15-F(2t)-IsoP-d(4) from co-eluting peaks. It was hypothesized that interfering peaks at m/z 573 could be the tetrahydro analogue of 15-F(2t)-IsoP. However, using an authentic standard showed the interfering peaks are not due to this metabolite. In subsequent experiments good resolution was shown of the 15-F(2t)-IsoP peak using 8-F(2t)-IsoP-d(4) (m/z 573) as the internal standard. These data show that care must be taken when using GC-MS for quantitation of F(2)-IsoPs to prevent interfering substances affecting the results.

Dietary nitrate supplementation enhances cerebrovascular CO₂ reactivity in a sex-specific manner

Publisher: American Physiological Society

Date: 09-2019

DOI: 10.1152/JAPPLPHYSIOL.01116.2018

Abstract: Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction, and increased NO has the potential to enhance cerebral blood flow (CBF). Dietary supplementation with sodium nitrate, a precursor of NO, could improve cerebrovascular function, but this has not been investigated. In 17 in iduals, we examined the effects of a 7-day supplementation of dietary nitrate (0.1 mmol·kg −1 ·day −1 ) on cerebrovascular function using a randomized, single-blinded placebo-controlled crossover design. We hypothesized that 7-day dietary nitrate supplementation increases CBF response to CO 2 (cerebrovascular CO 2 reactivity) and cerebral autoregulation (CA). We assessed middle cerebral artery blood velocity (MCAv) and blood pressure (BP) at rest and during CO 2 breathing. Transfer function analysis was performed on resting beat-to-beat MCAv and BP to determine CA, from which phase, gain, and coherence of the BP-MCAv data were derived. Dietary nitrate elevated plasma nitrate concentration by ~420% ( P 0.001) and lowered gain ( d = 1.2, P = 0.025) and phase of the BP-MCAv signal compared with placebo treatment ( d = 0.7, P = 0.043), while coherence was unaffected ( P = 0.122). Dietary nitrate increased the MCAv-CO 2 slope in a sex-specific manner (interaction: P = 0.016). Dietary nitrate increased the MCAv-CO 2 slope in men ( d = 1.0, P = 0.014 vs. placebo), but had no effect in women ( P = 0.919). Our data demonstrate that dietary nitrate greatly increased cerebrovascular CO 2 reactivity in healthy in iduals, while its effect on CA remains unclear. The selective increase in the MCAv-CO 2 slope observed in men indicates a clear sexual dimorphic role of NO in cerebrovascular function. NEW & NOTEWORTHY We found dietary nitrate supplementation improved the brain blood vessels’ response to CO 2 , cerebrovascular CO 2 reactivity, without affecting blood pressure in a group of healthy in iduals. Meanwhile, the effect of dietary nitrate on the relationship between blood pressure and brain blood flow, cerebral autoregulation, was inconclusive. The improvement in cerebrovascular CO 2 reactivity was only observed in the male participants, alluding to a sex difference in the effect of dietary nitrate on brain blood flow control. Our findings indicate that dietary nitrate could be an effective strategy to enhance cerebrovascular CO 2 reactivity.

Disruption of hemochromatosis protein and transferrin receptor 2 causes iron-induced liver injury in mice.

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 11-06-2012

DOI: 10.1002/HEP.25689

Abstract: Mutations in hemochromatosis protein (HFE) or transferrin receptor 2 (TFR2) cause hereditary hemochromatosis (HH) by impeding production of the liver iron-regulatory hormone, hepcidin (HAMP). This study examined the effects of disruption of Hfe or Tfr2, either alone or together, on liver iron loading and injury in mouse models of HH. Iron status was determined in Hfe knockout (Hfe(-/-)), Tfr2 Y245X mutant (Tfr2(mut)), and double-mutant (Hfe(-/-) ×Tfr2(mut) ) mice by measuring plasma and liver iron levels. Plasma alanine transaminase (ALT) activity, liver histology, and collagen deposition were evaluated to assess liver injury. Hepatic oxidative stress was assessed by measuring superoxide dismutase (SOD) activity and F(2)-isoprostane levels. Gene expression was measured by real-time polymerase chain reaction. Hfe(-/-) ×Tfr2(mut) mice had elevated hepatic iron with a periportal distribution and increased plasma iron, transferrin saturation, and non-transferrin-bound iron, compared with Hfe(-/-), Tfr2(mut), and wild-type (WT) mice. H 1 expression was reduced to 40% (Hfe(-/-) and Tfr2(mut) ) and 1% (Hfe(-/-) ×Tfr2(mut)) of WT values. Hfe(-/-) ×Tfr2(mut) mice had elevated plasma ALT activity and mild hepatic inflammation with scattered aggregates of infiltrating inflammatory cluster of differentiation 45 (CD45)-positive cells. Increased hepatic hydoxyproline levels as well as Sirius red and Masson's Trichrome staining demonstrated advanced portal collagen deposition. Hfe(-/-) and Tfr2(mut) mice had less hepatic inflammation and collagen deposition. Liver F(2) -isoprostane levels were elevated, and copper/zinc and manganese SOD activities decreased in Hfe(-/-) ×Tfr2(mut), Tfr2(mut), and Hfe(-/-) mice, compared with WT mice. Disruption of both Hfe and Tfr2 caused more severe hepatic iron overload with more advanced lipid peroxidation, inflammation, and portal fibrosis than was observed with the disruption of either gene alone. The Hfe(-/-) ×Tfr2(mut) mouse model of iron-induced liver injury reflects the liver injury phenotype observed in human HH.

A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: The Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910)

Publisher: Springer Science and Business Media LLC

Date: 06-03-2012

DOI: 10.1186/1475-2891-11-11

The acute effect of coffee on endothelial function and glucose metabolism following a glucose load in healthy human volunteers

Publisher: Royal Society of Chemistry (RSC)

Date: 2017

DOI: 10.1039/C7FO00926G

Abstract: The consumption of coffee, as a whole beverage, may improve vascular function, although this may be due to the caffeine.

Antioxidant vitamins and adrenocorticotrophic hormone-induced hypertension in rats

Publisher: Informa UK Limited

Date: 2007

DOI: 10.1080/10641960701615774

Abstract: This study examined whether the anti-oxidants ascorbic acid, alpha- or gamma-tocopherol, could modify adrenocorticotrophic hormone (ACTH)-hypertension in Sprague-Dawley rats, a model associated with increased oxidative stress. Systolic blood pressure (SBP) was measured by the tail-cuff method. After four days of ascorbic acid (AA) (200 mg/kg/day drinking) or alpha-tocopherol (500 mg/kg/d i.p. or feed), rats were co-administered ACTH (0.2 mg/kg/day s.c.) or saline for 11 days (prevention studies). In reversal studies, ACTH/saline was administered for 15 days, and from day 9, alpha- or gamma-tocopherol (20 mg/kg/day) was added. ACTH increased SBP compared to saline (p < 0.05). AA or alpha-tocopherol failed to prevent and alpha- or gamma-tocopherol failed to reverse ACTH-induced hypertension. Thus, neither vitamin C (water soluble) nor E (lipid soluble) modified ACTH-induced hypertension in the rat.

Development of a reference database for assessing dietary nitrate in vegetables

Publisher: Wiley

Date: 03-05-2017

DOI: 10.1002/MNFR.201600982

Abstract: Nitrate from vegetables improves vascular health with short-term intake. Whether this translates into improved long-term health outcomes has yet to be investigated. To enable reliable analysis of nitrate intake from food records, there is a strong need for a comprehensive nitrate content of vegetables database. A systematic literature search (1980-2016) was performed using Medline, Agricola and Commonwealth Agricultural Bureaux abstracts databases. The nitrate content of vegetables database contains 4237 records from 255 publications with data on 178 vegetables and 22 herbs and spices. The nitrate content of in idual vegetables ranged from Chinese flat cabbage (median range: 4240 3004-6310 mg/kg FW) to corn (median range: 12 5-1091 mg/kg FW). The database was applied to estimate vegetable nitrate intake using 24-h dietary recalls (24-HDRs) and food frequency questionnaires (FFQs). Significant correlations were observed between urinary nitrate excretion and 24-HDR (r = 0.4, P = 0.013), between 24-HDR and 12 month FFQs (r = 0.5, P < 0.001) as well as two 4 week FFQs administered 8 weeks apart (r = 0.86, P < 0.001). This comprehensive nitrate database allows quantification of dietary nitrate from a large variety of vegetables. It can be applied to dietary records to explore the associations between nitrate intake and health outcomes in human studies.

Green coffee polyphenols do not attenuate features of the metabolic syndrome and improve endothelial function in mice fed a high fat diet

Publisher: Elsevier BV

Date: 10-2014

DOI: 10.1016/J.ABB.2014.02.005

Abstract: We have investigated the effects of the major polyphenol in coffee, chlorogenic acid (CGA), on obesity, glucose intolerance, insulin resistance, systemic oxidative stress and endothelial dysfunction in a mouse model of the metabolic syndrome. Thirty C57BL6 mice were randomly ided into (n=10/group) (i) normal diet (ND), (ii) high fat diet (HFD), or (iii) high fat diet supplemented with 0.5% w/w green coffee bean extract (GCE) rich in chlorogenic acid (HFD+GCE). The high fat diet consisted of 28% fat and all animals were maintained on their diets for 12 weeks. The mice fed a HFD and HFD+GCE displayed symptoms of the metabolic syndrome compared to their normal fed counterparts, although no endothelial dysfunction was detected in the abdominal aortas after 12 weeks. GCE did not attenuate HFD-induced obesity, glucose intolerance, insulin resistance or systemic oxidative stress. Furthermore, GCE did not protect against ex vivo oxidant (hypochlorous acid)-induced endothelial dysfunction.

Expression of Sterol 27-Hydroxylase (CYP27A1) Enhances Cholesterol Efflux

Publisher: Elsevier BV

Date: 03-2003

DOI: 10.1074/JBC.M212780200

Phenolic acid metabolites as biomarkers for tea- and coffee-derived polyphenol exposure in human subjects

Publisher: Cambridge University Press (CUP)

Date: 02-2004

DOI: 10.1079/BJN20031046

Abstract: Tea and coffee are rich in polyphenols with a variety of biological activities. Many of the demonstrated activities are consistent with favourable effects on the risk of chronic diseases. 4- O -methylgallic acid (4OMGA) and isoferulic acid are potential biomarkers of exposure to polyphenols derived from tea and coffee respectively. 4OMGA is derived from gallic acid in tea, and isoferulic acid is derived from chlorogenic acid in coffee. Our major objective was to explore the relationships of tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid in human subjects. The relationships of long-term usual (111 participants) and contemporaneously recorded current (344 participants) tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid were assessed in two populations. 4OMGA was related to usual ( r 0·50, P ·001) and current ( r 0·57, P ·001) tea intake, and isoferulic acid was related to usual ( r 0·26, P =0·008) and current ( r 0·18, P ·001) coffee intake. Overall, our present results are consistent with the proposal that 4OMGA is a good biomarker for black tea-derived polyphenol exposure, but isoferulic acid may be of limited usefulness as a biomarker for coffee-derived polyphenol exposure.

Parenteral lipid emulsions based on olive oil compared with soybean oil in preterm (

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 11-2009

DOI: 10.1097/MPG.0B013E31819CA1B8

Measurement of urinary F2-isoprostanes as markers of in vivo lipid peroxidation: a comparison of enzyme immunoassay with gas chromatography mass spectrometry

Publisher: Elsevier BV

Date: 08-1999

DOI: 10.1006/ABIO.1999.4187

Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes

Publisher: Elsevier BV

Date: 05-2003

DOI: 10.1016/S0021-9150(02)00417-3

Abstract: Arteriopathy is the principal complication of type 2 diabetes mellitus. It develops from endothelial dysfunction, which we have hypothesised occurs in diabetes primarily as a consequence of dyslipidaemia and oxidative stress. Fenofibrate and CoQ may improve endothelial function by regulating dyslipidaemia and oxidative stress, respectively. We therefore aimed to assess the independent and combined effects of fenofibrate and coenzyme Q(10) (CoQ) on endothelium-dependent and endothelium-independent vasodilator function of the forearm microcirculation in type 2 diabetes. Eighty dyslipidaemic type 2 diabetics were randomized to receive fenofibrate (200 mg/daily), CoQ (200 mg/daily), fenofibrate plus CoQ (200+200 mg daily), or placebo for 12 weeks. Forearm microcirculatory function was assessed with venous occlusion plethysmography during the infusion of acetylcholine (ACh), bradykinin (BK), sodium nitroprusside (SNP) and N(G)-monomethyl-L-arginine (L-NMMA) into the brachial artery. Blood flow responses were calculated as area under the curve (AUC). Fenofibrate significantly lowered plasma cholesterol, triglyceride and fibrinogen (P<0.001), and elevated HDL-cholesterol and homocysteine (P<0.001). CoQ did not change plasma isoprostanes, but significantly lowered systolic blood pressure and HbA(1c) (P<0.05). Fenofibrate plus CoQ significantly improved (P<0.05) the AUC for ACh, BK and SNP without significantly altering basal responses to L-NMMA. Fenofibrate or CoQ alone did not significantly alter blood flow responses. Improvements in blood flow were independent of changes in plasma lipids, blood pressure, homocysteine and isoprostanes, but were correlated (P=0.013) with HbA(1c). In conclusion, in this factorial trial we found that only the combination of fenofibrate and CoQ markedly improved endothelial and non-endothelial forearm vasodilator function in dyslipidemic type 2 diabetic patients. The favourable vascular effect of this therapeutic combination could be due to increase in the bioactivity of and/or responses to endothelium-derived relaxing factors, including nitric oxide, and this may entail synergistic stimulation of peroxisome proliferator-activated receptors.

Phenolic composition of 91 Australian apple varieties: towards understanding their health attributes

Publisher: Royal Society of Chemistry (RSC)

Date: 2020

DOI: 10.1039/D0FO01130D

Abstract: Apples, an important contributor to total dietary phenolic intake, are associated with cardiovascular health benefits.

Effect of N‐acetylcysteine supplementation on oxidative stress status and alveolar inflammation in people exposed to asbestos: A double‐blind, randomized clinical trial

Publisher: Wiley

Date: 14-07-2015

DOI: 10.1111/RESP.12592

Abstract: Many of the pathological consequences in the lung following inhalation of asbestos fibres arise as a consequence of persistent oxidative stress and inflammation. Inflammatory responses can be observed in asymptomatic asbestos-exposed in iduals. There are currently no interventions to reduce inflammatory or oxidative responses to asbestos before disease develops. We investigated the effects of oral N-acetylcysteine (NAC) on indicators of inflammation or oxidative stress in asymptomatic people previously exposed to asbestos. A double-blind, randomized, placebo-controlled study was conducted to assess the effectiveness and safety of 1800 mg of NAC given orally over a period of 4 months. This was a proof of principle study. Effectiveness was assessed using indicators of inflammation or oxidation as primary end-points. Serum levels of total combined thiols (cysteine, cysteinylglycine, glutathione and homocysteine) were used to monitor the NAC supplementation. Thirty-four subjects were randomly allocated to NAC and 32 to placebo. Serum levels of total combined thiols were similar between the groups after intervention. There were no differences in levels of inflammatory or oxidative stress end-points between the groups. No adverse effects were identified. No evidence was found that NAC supplementation replenishes total combined thiols in the blood of healthy subjects with a history of asbestos exposure. There was also no evidence of reduced indicators of inflammation or oxidative stress. Further studies should determine the conditions required to increase levels of total anti-oxidant capacity in the blood and in the lungs of subjects with either asbestos-related diseases or subclinical lung inflammation.

Absence of an effect of high nitrate intake from beetroot juice on blood pressure in treated hypertensive individuals: A randomized controlled trial

Publisher: Elsevier BV

Date: 08-2015

DOI: 10.3945/AJCN.114.101188

Abstract: Dietary nitrate, which is in green leafy vegetables and beetroot, decreases blood pressure through the enterosalivary nitrate-nitrite-nitric oxide pathway in healthy in iduals. Whether similar effects would occur in in iduals with treated hypertension and, therefore, at increased risk of cardiovascular disease is unclear. We assessed whether increased dietary nitrate intake by using beetroot juice for 1 wk lowers blood pressure in treated hypertensive men and women. Participants (n = 27) were recruited to a randomized, placebo-controlled, double-blind crossover trial. The effect of 1-wk intake of nitrate-rich beetroot juice was compared with 1-wk intake of nitrate-depleted beetroot juice (placebo). The primary outcome was blood pressure assessed by measuring home blood pressure during the intervention and 24-h ambulatory blood pressure on day 7 of the intervention. Other outcomes included nitrate metabolism assessed by measuring nitrate and nitrite in plasma, saliva, and urine. Relative to the placebo, 1-wk intake of nitrate-rich beetroot juice resulted in a 3-fold increase in plasma nitrite and nitrate, a 7-fold increase in salivary nitrite, an 8-fold higher salivary nitrate, and a 4-fold increase in both urinary nitrite and nitrate (P < 0.001). However, no differences in home blood pressure and 24-h ambulatory blood pressure were observed with 1-wk intake of nitrate-rich beetroot juice in comparison with the placebo. An increase in dietary nitrate intake may not be an effective short-term approach to further lower blood pressure in treated hypertensive subjects.

Flavonoid intake is associated with lower mortality in the Danish Diet Cancer and Health Cohort

Publisher: Springer Science and Business Media LLC

Date: 13-08-2019

DOI: 10.1038/S41467-019-11622-X

Abstract: Flavonoids, plant-derived polyphenolic compounds, have been linked with health benefits. However, evidence from observational studies is incomplete studies on cancer mortality are scarce and moderating effects of lifestyle risk factors for early mortality are unknown. In this prospective cohort study including 56,048 participants of the Danish Diet, Cancer, and Health cohort crosslinked with Danish nationwide registries and followed for 23 years, there are 14,083 deaths. A moderate habitual intake of flavonoids is inversely associated with all-cause, cardiovascular- and cancer-related mortality. This strong association plateaus at intakes of approximately 500 mg/day. Furthermore, the inverse associations between total flavonoid intake and mortality outcomes are stronger and more linear in smokers than in non-smokers, as well as in heavy ( g/d) vs. low-moderate ( g/d) alcohol consumers. These findings highlight the potential to reduce mortality through recommendations to increase intakes of flavonoid-rich foods, particularly in smokers and high alcohol consumers.

Evidence for the nitration of gamma-tocopherol in vivo: 5-nitro-gamma-tocopherol is elevated in the plasma of subjects with coronary heart disease.

Publisher: Portland Press Ltd.

Date: 15-06-2002

DOI: 10.1042/BJ20020491

Abstract: This study investigated the hypothesis that nitration of γ-tocopherol may be an important mechanism for the detoxification of reactive nitrogen oxide species in vivo. Using liquid chromatography—tandem MS we have shown that γ-tocopherol can be nitrated in vivo to form 5-nitro-γ-tocopherol and that concentrations of this compound are elevated in the plasma of subjects with coronary heart disease. In addition, we demonstrate in carotid-artery atherosclerotic plaque that nitration of γ-tocopherol is also evident at levels similar to that seen in the plasma of subjects with coronary heart disease.

Long-term dietary nitrate supplementation slows the progression of established atherosclerosis in ApoE−/− mice fed a high fat diet

Publisher: Springer Science and Business Media LLC

Date: 28-02-2023

DOI: 10.1007/S00394-023-03127-7

Abstract: Atherosclerosis is associated with a reduction in the bioavailability and/or bioactivity of endogenous nitric oxide (NO). Dietary nitrate has been proposed as an alternate source when endogenous NO production is reduced. Our previous study demonstrated a protective effect of dietary nitrate on the development of atherosclerosis in the apoE −/− mouse model. However most patients do not present clinically until well after the disease is established. The aims of this study were to determine whether chronic dietary nitrate supplementation can prevent or reverse the progression of atherosclerosis after disease is already established, as well as to explore the underlying mechanism of these cardiovascular protective effects. 60 apoE −/− mice were given a high fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis. The mice were then randomized to (i) control group (HFD + 1 mmol/kg/day NaCl), (ii) moderate-dose group (HFD +1 mmol/kg/day NaNO3), or (iii) high-dose group (HFD + 10 mmol/kg/day NaNO3) (20/group) for a further 12 weeks. A group of apoE −/− mice (n = 20) consumed a normal laboratory chow diet for 24 weeks and were included as a reference group. Long-term supplementation with high dose nitrate resulted in ~ 50% reduction in plaque lesion area. Collagen expression and smooth muscle accumulation were increased, and lipid deposition and macrophage accumulation were reduced within atherosclerotic plaques of mice supplemented with high dose nitrate. These changes were associated with an increase in nitrite reductase as well as activation of the endogenous eNOS-NO pathway. Long-term high dose nitrate significantly attenuated the progression of established atherosclerosis in the apoE −/− mice fed a HFD. This appears to be mediated in part through a XOR-dependent reduction of nitrate to NO, as well as enhanced eNOS activation via increased Akt and eNOS phosphorylation.

The antioxidant tempol prevents and partially reverses dexamethasone-induced hypertension in the rat

Publisher: Oxford University Press (OUP)

Date: 03-2004

DOI: 10.1016/J.AMJHYPER.2003.11.004

Dietary nitrate reduces blood pressure and cerebral artery velocity fluctuations and improves cerebral autoregulation in transient ischemic attack patients

Publisher: American Physiological Society

Date: 09-2020

DOI: 10.1152/JAPPLPHYSIOL.00160.2020

Abstract: We found dietary nitrate supplementation reduced blood pressure and brain blood flow fluctuations and improved the relationship between blood pressure and brain blood flow in transient ischemic attack patients. Meanwhile, dietary nitrate had no effects on the brain blood vessels’ response to CO 2 . We attribute the improved brain blood flow stability to the improved myogenic control of blood pressure with dietary nitrate. Our findings indicate that dietary nitrate could be an effective strategy for stabilizing blood pressure and brain blood flow following transient ischemic attack.

Tolerability and safety of olive oil–based lipid emulsion in critically ill neonates: A blinded randomized trial

Publisher: Elsevier BV

Date: 11-2008

DOI: 10.1016/J.NUT.2008.05.004

Abstract: We assessed the safety and tolerability of an olive oil-based lipid emulsion compared with a soybean-based lipid emulsion in critically ill neonates. A double-blinded, randomized study was conducted in critically ill neonates requiring parenteral nutrition in the first week of life. Infants were randomized to receive a lipid emulsion based on olive oil (OO ClinOleic) or soybean oil (SO Intralipid) for a minimum of 5 d. Plasma phospholipid fatty acids, F(2)-isoprostanes, liver function, and clinical outcome were assessed after 5 d of therapy. Seventy-eight neonates (men gestational age 37 wk, range 26-41 wk) received OO (n = 39) or SO (n = 39). Both emulsions were well tolerated with no adverse events observed. At day 5, plasma phospholipid oleic acid (C18:1omega-9) levels increased in infants receiving OO compared with lower levels in infants receiving SO (mean percentage +/- SD 33.1 +/- 6.4 for OO versus 18.6 +/- 2.4 for SO mean difference -14.7 mmol/L, 95% confidence interval -17.5 to -11.9). The increase in plasma phospholipid linoleic acid levels was attenuated in infants receiving OO (mean percentage +/- SD 12.6 +/- 3.0 for OO versus 23.7 +/- 6.9 for SO adjusted mean 11.4 mmol/L, 95% confidence interval 8.1-14.8). No differences were observed in plasma F(2)-isoprostane levels according to the type of lipid emulsion received. The OO-based emulsion (ClinOleic) was well tolerated in critically ill neonates. Differences in plasma phospholipids at day 5 reflected the fatty acid composition of the administered emulsion. No significant differences in plasma F(2)-isoprostane levels were detected after 5 d of lipid administration.

Kidney expression of glutathione peroxidase-1 is not protective against streptozotocin-induced diabetic nephropathy

Publisher: American Physiological Society

Date: 09-2005

DOI: 10.1152/AJPRENAL.00088.2005

Abstract: In many diseases, including progressive renal disorders, tissue injury and pathological intracellular signaling events are dependent on oxidative stress. Glutathione peroxidase-1 (Gpx1) is an antioxidant enzyme that is highly expressed in the kidney and removes peroxides and peroxynitrite that can cause renal damage. Therefore, we examined whether this abundant renal antioxidant enzyme limits renal damage during the development of type 1 diabetic nephropathy. Wild-type (Gpx1+/+) and deficient (Gpx1−/−) mice were made diabetic by intraperitoneal injection of streptozotocin (100 mg/kg) on 2 consecutive days. Diabetic Gpx1+/+ and −/− mice with equivalent blood glucose levels (23 ± 4 mM) were selected and examined after 4 mo of diabetes. Compared with normal mice, diabetic Gpx1+/+ and −/− mice had a two- to threefold increase in urine albumin excretion at 2 and 4 mo of diabetes. At 4 mo, diabetic Gpx1+/+ and −/− mice had equivalent levels of oxidative renal injury (increased kidney reactive oxygen species, kidney lipid peroxidation, urine isoprostanes, kidney deposition of advanced glycoxidation, and nitrosylation end products) and a similar degree of glomerular damage (hypertrophy, hypercellularity, sclerosis), tubular injury (apoptosis and vimentin expression), and renal fibrosis (myofibroblasts, collagen, TGF-β excretion). A lack of Gpx1 was not compensated for by increased levels of catalase or other Gpx isoforms in diabetic kidneys. Contrary to expectations, this study showed that the high level of Gpx1 expressed in the kidney is not protective against the development of renal oxidative stress and nephropathy in a model of type 1 diabetes.

Regular consumption of black tea increases circulating kynurenine concentrations: a randomized controlled trial

Publisher: Elsevier BV

Date: 06-2015

DOI: 10.1016/J.BBACLI.2014.11.007

Effect of repeat-sprint training in hypoxia on post-exercise interleukin-6 and F₂-isoprostanes

Publisher: Informa UK Limited

Date: 22-12-2015

DOI: 10.1080/17461391.2015.1123776

Abstract: This investigation examined the oxidative stress (F2-Isoprostane F2-IsoP) and inflammatory (interleukin-6 IL-6) responses to repeat-sprint training in hypoxia (RSH). Ten trained male team sport athletes performed 3(sets)*9(repetitions)*5 s cycling sprints in simulated altitude (3000 m) and sea-level conditions. Mean and peak sprint power output (MPO and PPO) were recorded, and blood s les were collected pre-exercise, and again at 8 and 60 min post-exercise. Both MPO and PPO were significantly reduced in hypoxia (compared to sea-level) in the second (MPO: 855 ± 89 vs. 739 ± 95 W, p = .006 PPO: 1024 ± 114 vs. 895 ± 112 W, p = .010) and third (MPO: 819 ± 105 vs. 686 ± 83 W, p = .008 PPO: 985 ± 125 vs. 834 ± 99 W, p = .008) sets, respectively. IL-6 was significantly increased from pre- to 1 h post-exercise in both hypoxia (0.7 ± 0.2 vs. 2.4 ± 1.4 pg/mL, p = .004) and sea-level conditions (0.7 ± 0.2 vs. 1.6 ± 0.3 pg/mL, p < .001), with a large effect (d = 0.80) suggesting higher IL-6 levels of post-hypoxia. F2-IsoP was significantly lower 1 h post-exercise in both the hypoxic (p = .005) and sea-level (p = .002) conditions, with no differences between trials. While hypoxia can impact on exercise intensity and may result in greater post-exercise inflammation, it appears to have little effect on oxidative stress. These results indicate that team sport organisations with ready access to hypoxic training facilities could confidently administer RSH without significantly increasing the post-exercise inflammatory or oxidative stress response.

Effects of Sepiapterin Supplementation and NOS Inhibition on Glucocorticoid-Induced Hypertension

Publisher: Oxford University Press (OUP)

Date: 05-2010

DOI: 10.1038/AJH.2010.27

Abstract: Glucocorticoid-induced hypertension is associated with imbalance between nitric oxide (NO) and superoxide. One of the pathways that causes this imbalance is endothelial NO synthase (eNOS) uncoupling. In the present study, adrenocorticotrophic hormone (ACTH)- and dexamethasone-treated rats were further treated with sepiapterin, a precursor of tetrahydrobiopterin, or N-nitro-L-arginine (NOLA), an inhibitor of NOS, to investigate the role of eNOS uncoupling in glucocorticoid-induced hypertension. Male Sprague-Dawley (SD) rats (n = 7-13/group) were treated with either sepiapterin (5 mg/kg/day, IP) or saline (sham) 4 days before and during ACTH (0.2 mg/kg/day, SC), dexamethasone (0.03 mg/kg/day, SC), or saline treatment. NOLA (0.4 mg/ml in drinking water) was given to rats 4 days before and during dexamethasone treatment. Systolic blood pressure (SBP) was measured by the tail-cuff method. Both ACTH (116 +/- 2 to 135 +/- 3 mm Hg (mean +/- s.e.m.), P < 0.001) and dexamethasone (114 +/- 4 to 133 +/- 3 mm Hg, P < 0.0005) increased SBP. Sepiapterin alone did not alter SBP. Sepiapterin did not prevent ACTH- (129 +/- 4 mm Hg, NS) or dexamethasone-induced hypertension (135 +/- 3 mm Hg, NS), although plasma total biopterin concentrations were increased. NOLA increased SBP in rats prior to dexamethasone or saline treatment. NOLA further increased SBP in both saline- (133 +/- 4 to 157 +/- 3 mm Hg, P < 0.05) and dexamethasone-treated rats (135 +/- 5 to 170 +/- 6 mm Hg, P < 0.05). ACTH and dexamethasone increased plasma F(2)-isoprostane concentrations. Neither sepiapterin nor NOLA significantly affected this marker of oxidative stress. Sepiapterin did not prevent ACTH- or dexamethasone-induced hypertension. NOLA exacerbated dexamethasone-induced hypertension. These data suggest that eNOS uncoupling does not play a major role in the genesis of glucocorticoid-induced hypertension in the rat.

Inhibition of 20-Hydroxyeicosatetraenoic Acid Synthesis using Specific Plant Lignans. In Vitro and Human Studies

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 11-2009

DOI: 10.1161/HYPERTENSIONAHA.109.139352

Abstract: Sesamin, the major lignan found in sesame, has been shown to increase vitamin E levels by inhibiting its metabolism via the cytochrome P 450 isozyme CYP4F2. CYP4F2 and CYP4A11 are the predominant human isoforms that synthesize 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid. Considerable evidence suggests that 20-HETE may play a role in the pathogenesis of hypertension. We hypothesized that sesamin could be an inhibitor of 20-HETE synthesis. This study investigated the effects of sesamin on 20-HETE synthesis in vitro and the effect of sesame supplementation on plasma and urinary 20-HETE concentrations in humans. Human microsomes were used to investigate the potency and selectivity of sesamin inhibition of 20-HETE synthesis. Sesamin inhibited human renal and liver microsome 20-HETE synthesis with IC 50 μmol/L. It was selective toward CYP4F2 (IC 50 : 1.9 μmol/L) and had reduced activity toward CYP4A11 (IC 50 : μmol/L), as well as cytochrome P epoxygenation of arachidonic acid (IC 50 : μmol/L). In a randomized, controlled crossover trial, overweight men and women (n=33) consumed 25 g/d of sesame (≈50 mg/d of sesame lignan) or an isocaloric matched control for 5 weeks each. Relative to control, sesame supplementation resulted in a 28% decrease in plasma and a 32% decrease in urinary 20-HETE ( P .001). Urinary sodium, potassium, and blood pressure were not affected. This study demonstrates for the first time that sesame supplementation in humans reduces the plasma and urinary levels of 20-HETE, likely via inhibition of CYP4F2 by sesame lignans. These results suggest that sesame lignans could be used for the investigation of potential roles of 20-HETE in humans.

Flavonoid intake and all-cause mortality

Publisher: Elsevier BV

Date: 05-2015

DOI: 10.3945/AJCN.113.073106

Abstract: Flavonoids are bioactive compounds found in foods such as tea, chocolate, red wine, fruit, and vegetables. Higher intakes of specific flavonoids and flavonoid-rich foods have been linked to reduced mortality from specific vascular diseases and cancers. However, the importance of flavonoids in preventing all-cause mortality remains uncertain. The objective was to explore the association between flavonoid intake and risk of 5-y mortality from all causes by using 2 comprehensive food composition databases to assess flavonoid intake. The study population included 1063 randomly selected women aged >75 y. All-cause, cancer, and cardiovascular mortalities were assessed over 5 y of follow-up through the Western Australia Data Linkage System. Two estimates of flavonoid intake (total flavonoidUSDA and total flavonoidPE) were determined by using food composition data from the USDA and the Phenol-Explorer (PE) databases, respectively. During the 5-y follow-up period, 129 (12%) deaths were documented. Participants with high total flavonoid intake were at lower risk [multivariate-adjusted HR (95% CI)] of 5-y all-cause mortality than those with low total flavonoid consumption [total flavonoidUSDA: 0.37 (0.22, 0.58) total flavonoidPE: 0.36 (0.22, 0.60)]. Similar beneficial relations were observed for both cardiovascular disease mortality [total flavonoidUSDA: 0.34 (0.17, 0.69) flavonoidPE: 0.32 (0.16, 0.61)] and cancer mortality [total flavonoidUSDA: 0.25 (0.10, 0.62) flavonoidPE: 0.26 (0.11, 0.62)]. Using the most comprehensive flavonoid databases, we provide evidence that high consumption of flavonoids is associated with reduced risk of mortality in older women. The benefits of flavonoids may extend to the etiology of cancer and cardiovascular disease.

Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis

Publisher: Elsevier BV

Date: 05-2015

DOI: 10.1016/J.ABB.2015.03.008

Abstract: Atherosclerosis is characterised by the accumulation of lipids within macrophages in the artery wall. Low-density lipoprotein (LDL) is the source of this lipid, owing to the uptake of oxidised LDL by scavenger receptors. Myeloperoxidase (MPO) released by leukocytes during inflammation produces oxidants that are implicated in atherosclerosis. Modification of LDL by the MPO oxidant hypochlorous acid (HOCl), results in extensive lipid accumulation by macrophages. However, the reactivity of the other major MPO oxidant, hypothiocyanous acid (HOSCN) with LDL is poorly characterised, which is significant given that thiocyanate is the favoured substrate for MPO. In this study, we comprehensively compare the reactivity of HOCl and HOSCN with LDL, and show key differences in the profile of oxidative damage observed. HOSCN selectively modifies Cys residues on apolipoprotein B100, and oxidises cholesteryl esters resulting in formation of lipid hydroperoxides, 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and F2-isoprostanes. The modification of LDL by HOSCN results macrophage lipid accumulation, though generally to a lesser extent than HOCl-modified LDL. This suggests that a change in the ratio of HOSCN:HOCl formation by MPO from variations in plasma thiocyanate levels, will influence the nature of LDL oxidation in vivo, and has implications for the progression of atherosclerosis.

Development of a Food Composition Database for Assessing Nitrate and Nitrite Intake from Animal-based Foods

Publisher: Wiley

Date: 28-08-2230

DOI: 10.1002/MNFR.202100272

Abstract: Nitrate and nitrite are approved food additives in some animal‐based food products. However, nitrate and nitrite in foods are strictly regulated due to health concerns over methaemoglobinaemia and the potential formation of carcinogenic nitrosamines. In contrast, plants (like leafy vegetables) naturally accumulate nitrate ions a growing body of research reveals beneficial metabolic effects of nitrate via its endogenous conversion to nitric oxide. To refine the association of dietary nitrate and nitrite intake with health outcomes, reliable measures of nitrate and nitrite intake from dietary food records are required. While a vegetable nitrate content database has been developed, there is a need for a comprehensive up‐to‐date nitrate and nitrite content database of animal‐based foods. A systematic literature search (1980–September 2020) on the nitrate and nitrite content of animal‐based foods is carried out. Nitrate and nitrite concentration data and other relevant information are extracted and compiled into a database. The database contains 1921 entries for nitrate and 2077 for nitrite, extracted from 193 publications. The highest median nitrate content is observed in chorizo (median [IQR] 101.61 [60.05–105.93] mg kg ‐1 ). Canned fish products have the highest median nitrite level (median [IQR] 20.32 [6.16–30.16] mg kg ‐1 ). By subgroup, the median nitrate value in industrial processed meat products (e.g., uncured burger, patties and sausages), whole milk powder and in particular red meat are higher than cured meat products. Processed meat products from high‐income regions have lower median nitrate and nitrite content than those of middle‐income regions. This database can now be used to investigate the associations between nitrate and nitrite dietary intake and health outcomes in clinical trials and observational studies.

Overfeeding reduces insulin sensitivity and increases oxidative stress, without altering markers of mitochondrial content and function in humans

Publisher: Public Library of Science (PLoS)

Date: 07-05-2012

DOI: 10.1371/JOURNAL.PONE.0036320

Dietary Nitrate, Nitric Oxide, and Cardiovascular Health

Publisher: Informa UK Limited

Date: 15-05-2016

DOI: 10.1080/10408398.2013.811212

Abstract: Emerging evidence strongly suggests that dietary nitrate, derived in the diet primarily from vegetables, could contribute to cardiovascular health via effects on nitric oxide (NO) status. NO plays an essential role in cardiovascular health. It is produced via the classical L-arginine-NO-synthase pathway and the recently discovered enterosalivary nitrate-nitrite-NO pathway. The discovery of this alternate pathway has highlighted dietary nitrate as a candidate for the cardioprotective effect of a diet rich in fruit and vegetables. Clinical trials with dietary nitrate have observed improvements in blood pressure, endothelial function, ischemia-reperfusion injury, arterial stiffness, platelet function, and exercise performance with a concomitant augmentation of markers of NO status. While these results are indicative of cardiovascular benefits with dietary nitrate intake, there is still a lingering concern about nitrate in relation to methemoglobinemia, cancer, and cardiovascular disease. It is the purpose of this review to present an overview of NO and its critical role in cardiovascular health to detail the observed vascular benefits of dietary nitrate intake through effects on NO status as well as to discuss the controversy surrounding the possible toxic effects of nitrate.

Chemistry and biological effects of dietary phenolic compounds: Relevance to cardiovascular disease

Publisher: Wiley

Date: 11-03-2000

DOI: 10.1046/J.1440-1681.2000.03214.X

Abstract: 1. There has been considerable recent interest in the possibility that increased intake of dietary anti-oxidants may protect against cardiovascular disease. This is partly due to the knowledge that oxidative events in vivo may play a role in the pathogenesis of atherosclerosis. 2. While dietary anti-oxidants, such as vitamins E and C, have received considerable attention in this regard, relatively little is known about a similar anti-oxidant role for plant-derived polyphenolic compounds, such as the flavonoids and phenolic acids. A review of the distribution, bioavailability and biological activity of these compounds suggests that they may have a physiological role as anti-oxidants. 3. Human trials on the anti-oxidant effects of beverages rich in polyphenolics, such as red wine, fruit juice or tea, have been limited and results are, at present, inconclusive. This is due, in part, to poor methodologies available to measure oxidative damage in vivo. 4. There is a sound rationale for considering polyphenolics as important contributors to the dietary anti-oxidant intake derived from fruits and vegetables. However, continuing research is needed using appropriate biomarkers of oxidant damage in vivo before these compounds can be conclusively considered as dietary anti-oxidants with nutritional benefit.

Fruit intake and abdominal aortic calcification in elderly women: A prospective cohort study

Publisher: MDPI AG

Date: 10-03-2016

DOI: 10.3390/NU8030159

Antiplasmodial and antioxidant isofuranonaphthoquinones from the roots of Bulbine capitata.

Publisher: Georg Thieme Verlag KG

Date: 2001

DOI: 10.1055/S-2001-14329

Abstract: The roots of B. capitata yielded the new compounds 5,8-dihydroxy-1-tigloylmethylnaphtho[2,3-c]furan-4,9-dione, 1-acetoxymethyl-8-hydroxynaphtho[2,3-c]furan-4,9-dione, and 1-acetoxymethyl-5,8-dihydroxynaphtho[2,3-c]furan-4,9-dione, in addition to the known compounds chrysophanol, 10,10'-chrysophanol bianthrone, 8-hydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione, 5,8-dihydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione, 5,8-dihydroxy-1-hydroxymethylnaphtho[2,3-c]furan-4,9-dione, and 8-hydroxy-5-methoxy-1-methylnaphtho[2,3-c]furan-4,9-dione, or 5-hydroxy-8-methoxy-1-methylnaphtho[2,3-c]furan-4,9-dione. The new as well as the known isofuranonaphthoquinones showed antioxidant and weak antiplasmodial activities.

Nitrate-rich vegetables do not lower blood pressure in individuals with mildly elevated blood pressure: a 4-wk randomized controlled crossover trial

Publisher: Elsevier BV

Date: 06-2018

DOI: 10.1093/AJCN/NQY061

Abstract: Emerging evidence suggests that increasing intakes of nitrate-rich vegetables may be an effective approach to reduce blood pressure. Our primary aim was to determine whether daily consumption of nitrate-rich vegetables over 4 wk would result in lower blood pressure. Thirty participants with prehypertension or untreated grade 1 hypertension were recruited to a randomized controlled crossover trial with 4-wk treatment periods separated by 4-wk washout periods. Participants completed 3 treatments in random order: 1) increased intake (∼200 g/d) of nitrate-rich vegetables [high-nitrate (HN) ∼150 mg nitrate/d], 2) increased intake (∼200 g/d) of nitrate-poor vegetables [low-nitrate (LN) ∼22 mg nitrate/d], and 3) no increase in vegetables (control ∼6 mg nitrate/d). Compliance was assessed with the use of food diaries and by measuring plasma nitrate and carotenoids. Nitrate metabolism was assessed with the use of plasma, salivary, and urinary nitrate and nitrite concentrations. The primary outcome was blood pressure assessed by using 24-h ambulatory, home, and clinic measurements. Secondary outcomes included measures of arterial stiffness. Plasma nitrate and nitrite concentrations increased with the HN treatment in comparison to the LN and control treatments (P < 0.001). Plasma carotenoids increased with the HN and LN treatments compared with the control (P 0.05) after adjustment for pretreatment values, treatment period, and treatment order. Similarly, no differences were observed between treatments for arterial stiffness measures (P > 0.05). Increased intake of nitrate-rich vegetables did not lower blood pressure in prehypertensive or untreated grade 1 hypertensive in iduals when compared with increased intake of nitrate-poor vegetables and no increase in vegetables. This trial was registered at www.anzctr.org.au as ACTRN12615000194561.

Impaired verbal episodic memory in healthy older adults is marked by increased F 2 -Isoprostanes

Publisher: Elsevier BV

Date: 02-2018

DOI: 10.1016/J.PLEFA.2018.02.001

Abstract: Age-associated cognitive decline amongst otherwise healthy older in iduals is a multifaceted characteristic of ageing. The role of oxidative stress biomarkers has been increasingly examined in the context of pathological aging conditions that affect cognition. Plasma F

Hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 studied with a stable isotope technique in men with visceral obesity

Publisher: Springer Science and Business Media LLC

Date: 05-1998

DOI: 10.1038/SJ.IJO.0800602

Abstract: To test the hypothesis that the hepatic secretion of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apoB) is increased in men with visceral obesity and to examine whether the oversecretion of this apolipoprotein is related to insulin resistance and increased hepatic availability of lipid substrates. 16 obese men (body mass index (BMI) > 30 kg/m2, waist circumference > 100 cm) and 16 non-obese, age matched men, were studied. The hepatic secretion of VLDL apoB was measured using a primed (1 mg/kg), constant (1 mg/kg/h), intravenous infusion of 1-[13C]-leucine. Isotopic enrichment of VLDL apoB was determined using gas-chromatography mass spectrometry and a multi-compartmental model (SAAM-II) was used to estimate the fractional turnover rate of VLDL apoB. Plasma concentrations of total cholesterol, triglyceride, glucose, insulin, mevalonic acid and lathosterol, as well as dietary fat intake, were significantly higher (P < 0.05) in obese than control subjects. The obese subjects had significantly lower high-density-lipoprotein cholesterol (P < 0.01). VLDL apoB pool size and hepatic secretion rate (mg/kg fat free mass/d) were significantly higher in the obese than non-obese subjects (P < 0.02). The fractional catabolic rate of VLDL apoB was lower in the obese subjects compared with controls, but the difference did not attain conventional significance (P=0.053). In pooled analysis, there was a significant positive association (P < 0.05) between VLDL apoB secretion rate (mg/kg fat free mass/d) and waist-to-hip ratio (WHR), waist circumference, and fasting plasma triglyceride, insulin and glucose concentrations. In multiple linear regression analysis, the association between VLDL apoB secretion and fasting insulin concentration was independent of age, apolipoprotein E (apoE) genotype, mevalonic acid concentration, free fatty acid concentration and fat intake. Our findings are consistent with the hypothesis that in visceral obesity, insulin resistance and the associated increased lipid substrate supply to the liver contribute to hepatic oversecretion of apoB expansion in the VLDL apoB pool size may also be due to a catabolic defect related to insulin resistance.

Protein thiol oxidation does not change in skeletal muscles of aging female mice

Publisher: Springer Science and Business Media LLC

Date: 06-12-2014

DOI: 10.1007/S10522-013-9483-Y

Abstract: Oxidative stress caused by reactive oxygen species is proposed to cause age related muscle wasting (sarcopenia). Reversible oxidation of protein thiols by reactive oxygen species can affect protein function, so we evaluated whether muscle wasting in normal aging was associated with a pervasive increase in reversible oxidation of protein thiols or with an increase in irreversible oxidative damage to macromolecules. In gastrocnemius muscles of C57BL/6J female mice aged 3, 15, 24, 27, and 29 months there was no age related increase in protein thiol oxidation. In contrast, there was a significant correlation (R (2) = 0.698) between increasing protein carbonylation, a measure of irreversible oxidative damage to proteins, and loss of mass of gastrocnemius muscles in aging female mice. In addition, there was an age-related increase in lipofuscin content, an aggregate of oxidised proteins and lipids, in quadriceps limb muscles in aging female mice. However, there was no evidence of an age-related increase in malondialdehyde or F2-isoprostanes levels, which are measures of oxidative damage to lipids, in gastrocnemius muscles. In summary, this study does not support the hypothesis that a pervasive increase in protein thiol oxidation is a contributing factor to sarcopenia. Instead, the data are consistent with an aging theory which proposes that molecular damage to macromolecules leads to the structural and functional disorders associated with aging.

Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome

Publisher: American Diabetes Association

Date: 03-2003

DOI: 10.2337/DIABETES.52.3.803

Abstract: The metabolic syndrome is characterized by insulin resistance and abnormal apolipoprotein AI (apoAI) and apolipoprotein B-100 (apoB) metabolism that may collectively accelerate atherosclerosis. The effects of atorvastatin (40 mg/day) and micronised fenofibrate (200 mg/day) on the kinetics of apoAI and apoB were investigated in a controlled cross-over trial of 11 dyslipidemic men with the metabolic syndrome. ApoAI and apoB kinetics were studied following intravenous d3-leucine administration using gas-chromatography mass spectrometry with data analyzed by compartmental modeling. Compared with placebo, atorvastatin significantly decreased (P & 0.001) plasma concentrations of cholesterol, triglyceride, LDL cholesterol, VLDL apoB, intermediate-density lipoprotein (IDL) apoB, and LDL apoB. Fenofibrate significantly decreased (P & 0.001) plasma triglyceride and VLDL apoB and elevated HDL2 cholesterol (P & 0.001), HDL3 cholesterol (P & 0.01), apoAI (P = 0.01), and apoAII (P & 0.001) concentrations, but it did not significantly alter LDL cholesterol. Atorvastatin significantly increased (P & 0.002) the fractional catabolic rate (FCR) of VLDL apoB, IDL apoB, and LDL apoB but did not affect the production of apoB in any lipoprotein fraction or in the turnover of apoAI. Fenofibrate significantly increased (P & 0.01) the FCR of VLDL, IDL, and LDL apoB but did not affect the production of VLDL apoB. Relative to placebo and atorvastatin, fenofibrate significantly increased the production (P & 0.001) and FCR (P = 0.016) of apoAI. Both agents significantly lowered plasma triglycerides and apoCIII concentrations, but only atorvastatin significantly lowered (P & 0.001) plasma cholesteryl ester transfer protein activity. Neither treatment altered insulin resistance. In conclusion, these differential effects of atorvastatin and fenofibrate on apoAI and apoB kinetics support the use of combination therapy for optimally regulating dyslipoproteinemia in the metabolic syndrome.

Association of dietary nitrate with atherosclerotic vascular disease mortality: a prospective cohort study of older adult women

Publisher: Elsevier BV

Date: 07-2017

DOI: 10.3945/AJCN.116.146761

Impaired ex Vivo leukotriene B4 production characterizes the metabolic syndrome and is improved after weight reduction

Publisher: The Endocrine Society

Date: 12-2007

DOI: 10.1210/JC.2007-1417

Abstract: Context: Neutrophil (polymorphonuclear neutrophil) production of leukotriene B4 (LTB4) may be associated with alterations in immune and inflammatory function that characterize the metabolic syndrome (MetS). Objective: We investigated whether polymorphonuclear neutrophil production of LTB4 and its metabolites 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxyl-LTB4 were altered in subjects with features of the MetS before and after weight reduction. Design, Setting, Patients, and Intervention: In a case-controlled comparison, men and postmenopausal women with features of the MetS were matched with controls. Subjects with MetS were then matched and randomly assigned to either a 12-wk weight reduction study followed by 4-wk weight stabilization or 16-wk weight maintenance. Main Outcome Measures: Measurements were performed at baseline and at the end of the 16-wk period. Stimulated neutrophil LTB4 and its metabolites were measured by HPLC. Results: In the case-controlled study, body mass index, waist circumference, blood pressure, fasting triglycerides, and glucose were all significantly increased in subjects with features of the MetS (P & 0.05). Production of LTB4 and 20-OH-LTB4 was significantly lower compared with controls (P & 0.005). The weight loss intervention resulted in a 4.6-kg reduction in body weight and 6.6-cm decrease in waist circumference relative to controls and a significant increase in LTB4 and 20-OH-LTB4. Conclusions: Subjects with features of the MetS have lower stimulated LTB4, which is not due to increased metabolism of LTB4. Weight reduction restored the production of neutrophil LTB4, suggesting that in addition to modifying cardiovascular risk, weight loss may also help with the management of perturbed inflammatory responses in overweight subjects.

A randomised controlled crossover trial investigating the short-term effects of different types of vegetables on vascular and metabolic function in middle-aged and older adults with mildly elevated blood pressure

Publisher: Springer Science and Business Media LLC

Date: 12-05-2020

DOI: 10.1186/S12937-020-00559-3

Abstract: A diet rich in fruits and vegetables is recommended for cardiovascular health. However, the majority of Australians do not consume the recommended number of vegetable servings each day. Furthermore, intakes of vegetables considered to have the greatest cardiovascular benefit are often very low. Results from prospective observational studies indicate that a higher consumption of cruciferous vegetables (e.g. broccoli, cabbage, cauliflower) is associated with lower cardiovascular disease risk. This may be due to the presence of specific nutrients and bioactive compounds found almost exclusively, or at relatively high levels, in cruciferous vegetables. Therefore, the aim of this randomised controlled crossover trial is to determine whether regular consumption of cruciferous vegetables results in short-term improvement in measures related to cardiovascular disease risk, including ambulatory blood pressure, arterial stiffness, glycaemic control, and circulating biomarkers of oxidative stress and inflammation. Twenty-five participants (50–75 years) with mildly elevated blood pressure (systolic blood pressure 120–160 mmHg) will complete two 2-week intervention periods in random order, separated by a 2-week washout period. During the intervention period, participants will consume 4 servings (~ 300 g) of cruciferous vegetables per day as a soup (~ 500–600 mL/day). The ‘control’ soup will consist of other commonly consumed vegetables (potato, sweet potato, carrot, pumpkin). Both soups will be approximately matched for energy, protein, fat, and carbohydrate content. All measurements will be performed at the beginning and end of each intervention period. The findings of this study will provide evidence regarding the potential cardiometabolic health benefits of cruciferous vegetables, which may contribute to the revision of dietary and clinical guidelines. The trial was registered with the Australian New Zealand Clinical Trial Registry on 19th September 2019 ( ACTRN12619001294145 ).

Relationship of dietary nitrate intake from vegetables with cardiovascular disease mortality: a prospective study in a cohort of older Australians

Publisher: Springer Science and Business Media LLC

Date: 20-09-2019

DOI: 10.1007/S00394-018-1823-X

Abstract: Short-term trials indicate inorganic nitrate and nitrate-rich vegetables may have vascular health benefits. However, few observational studies have explored the relationship between nitrate intake and long-term cardiovascular disease (CVD) outcomes. The primary aim of this study was to investigate the association of nitrate intake from vegetables with CVD mortality in a s le of older Australians. A subgroup of participants without diabetes or major CVD at baseline (1992-1994) were included from the Blue Mountains Eye Study, a population-based cohort study of men and women aged ≥ 49 years. Diets were evaluated using a validated food frequency questionnaire at baseline, 5 years and 10 years of follow-up. Vegetable nitrate intake was estimated using a comprehensive vegetable nitrate database. Cox proportional hazard regression was used to explore the association between vegetable nitrate intake and CVD mortality. During 14 years of follow-up, 188/2229 (8.4%) participants died from CVD. In multivariable-adjusted analysis, participants in quartile 2 [69.5-99.6 mg/day HR 0.53 (95% CI 0.35, 0.82)], quartile 3 [99.7-137.8 mg/day HR 0.51 (95% CI 0.32, 0.80)], and quartile 4 [> 137.8 mg/day HR 0.63 (95% CI 0.41, 0.95)] of vegetable nitrate intake had lower hazards for CVD mortality compared to participants in quartile 1 (< 69.5 mg/day). In older Australian men and women, vegetable nitrate intake was inversely associated with CVD mortality, independent of lifestyle and cardiovascular risk factors. These findings confirm a recent report that intake of vegetable nitrate lowers the risk of CVD mortality in older women and extend these findings to older men.

The role of 20-hydroxyeicosatetraenoic acid in adrenocorticotrophic hormone and dexamethasone-induced hypertension

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 08-2009

DOI: 10.1097/HJH.0B013E32832CC56C

The effects of a lupin-enriched diet on oxidative stress and factors influencing vascular function in overweight subjects

Publisher: Mary Ann Liebert Inc

Date: 15-11-2010

DOI: 10.1089/ARS.2010.3133

Abstract: A diet enriched in lupin kernel flour can lower blood pressure, but mechanisms responsible are unclear. Lupin is a source of polyphenols, protein, and L-arginine, factors that may influence blood pressure via effects on oxidative stress and vascular function. Therefore, we aimed to determine the effects of a lupin-enriched diet on oxidative stress and factors influencing vascular function as potential mechanisms for demonstrated benefits on blood pressure. Overweight men and women (n = 88) were recruited to a 16-week parallel-design study. Participants were randomly assigned to replace 15%-20% of their usual daily energy intake with white bread (control) or lupin kernel flour-enriched bread (lupin). All measurements were taken at baseline and 16 weeks. At baseline, plasma F₂-isoprostanes and 20-hydroxyeicosatetraenoic acid (20-HETE) were positively associated with blood pressure, and plasma nitrite was negatively associated with blood pressure (p < 0.05). For lupin relative to control, the estimated differences in plasma F₂-isoprostanes (45 pmol/L 95%CI: -68, 158), urinary F₂-isoprostanes (17 pmol/mmol creatinine 95%CI: -43, 76), plasma 20-HETE (75 pmol/L 95%CI: -91, 241), and plasma nitrite (-0.3 μmol/L 95%CI: -1.1, 0.4) were not significant. Although regular consumption of lupin-enriched bread can lower blood pressure, these results do not support for the hypothesis that this is via effects on oxidative stress or vascular function.

The effects of oxidation products of arachidonic acid and n3 fatty acids on vascular and platelet function

Publisher: Informa UK Limited

Date: 14-01-2011

DOI: 10.3109/10715762.2010.544730

Abstract: 15-F₂(t)-isoprostane (15-F₂(t)-IsoP), an oxidation product of arachidonic acid (AA), affects vascular and platelet function however, the bioactivity of other fatty acids oxidation products is unknown. This paper studied rat aortic vascular reactivity and human platelet aggregation in response to 14 oxidation products of AA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and α-linolenic acid (ALA) compared with 15-F₂(t)-IsoP. It also compared the F₂(t)-IsoPs profile in human platelets. EPA-derived 15-F₃(t)-IsoP constricted rat aorta less than 15-F₂(t)-IsoP, but none of the other oxidation products affected vascular reactivity. Only 15-F₂(t)-IsoP (10⁻⁴ M) directly affected platelet aggregation. 15-F₃(t)-IsoP, ent-16-F₁-phytoprostane (from ALA) and isofurans A and B (from AA) inhibited reversible aggregation to U46619. Unlike plasma, the platelet profile of F₂-IsoP showed that 8-F(2t)-IsoP were higher than 15-F₂(t)-IsoP. Unlike 15-F₂(t)-IsoP, the test compounds derived from fatty acids oxidation did not affect vascular or platelet function. Elevated platelet 8-F₂(t)-IsoP could limit 15-F₂(t)-IsoP-induced aggregation under conditions of oxidant stress.

Brachial artery vasomotor function is inversely associated with 24-h ambulatory blood pressure

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2004

DOI: 10.1097/00004872-200405000-00019

Abstract: Impaired endothelial function has been reported in hypertensive in iduals. The extent to which such changes reflect the co-existence of other cardiovascular disease risk factors rather than an independent association with blood pressure remains uncertain. To assess the relationship between brachial artery vasomotor function and ambulatory blood pressure in hypertensive in iduals and normotensive controls. We assessed 24-h ambulatory blood pressure and brachial artery endothelial and smooth muscle function in 155 patients with hypertension and 40 normotensive controls. The vasomotor functions were determined by ultrasonographic assessment of vasodilator responses to flow and sublingual glyceryl trinitrate, respectively. Patients with hypertension were categorized as either treated (n = 85) or untreated (n = 70), and further sub ided on the basis of either no or at least one other cardiovascular risk factor. These included hyperlipidaemia, smoking, diabetes or a previous coronary or cerebrovascular event. Age- and sex-adjusted flow-mediated and glyceryl trinitrate-mediated responses were not significantly different in hypertensive in iduals with respect to treatment status or the presence of risk factors when compared with controls. However, when data from all 195 study participants were pooled, 24-h ambulatory systolic blood pressure was inversely related to flow-mediated response (P = 0.002), and both systolic and diastolic blood pressure were inversely related to glyceryl trinitrate response (P < 0.001 and P = 0.009, respectively). Observed relationships were largely unaltered after further adjustment for body mass index, antihypertensive treatment or the presence of other risk factors. The finding of a direct and inverse relationship between the level of ambulatory blood pressure and flow-mediated and glyceryl trinitrate responses is consistent with a direct influence of blood pressure on conduit vessel vascular function.

Chlorogenic acid improves ex vivo vessel function and protects endothelial cells against HOCl-induced oxidative damage, via increased production of nitric oxide and induction of Hmox-1

Publisher: Elsevier BV

Date: 2016

DOI: 10.1016/J.JNUTBIO.2015.08.017

Abstract: Dietary polyphenols are potential contributors toward improved cardiovascular health. Coffee is one of the richest sources of dietary polyphenols in a coffee-drinking population, the most abundant form being chlorogenic acid (CGA). Endothelial dysfunction is an early and major risk factor for cardiovascular disease. Nitric oxide (NO) is a key factor in regulation of endothelial function. Heme oxygenase-1 (Hmox-1), an inducible isoform of heme oxygenase that is produced in response to stressors such as oxidative stress, may also play a role in vascular protection. The aim of this study was to investigate the effect of CGA on endothelial function with oxidant-induced damage in isolated aortic rings from C57BL mice. We further examine the mechanism by investigating cell viability, activation of eNOS and induction of Hmox-1 in human aortic endothelial cells (HAECs). We found that pretreatment of isolated aortic rings with 10-μM CGA-protected vessels against HOCl-induced endothelial dysfunction (P<0.05). Pretreatment of cultured HAECs with 10-μM CGA increased endothelial cell viability following exposure to HOCl (P<0.05). Moreover, CGA increased NO production in HAECs in a dose-dependent manner, peaking at 6 h (P<0.05). CGA at 5 μM and 10 μM increased eNOS dimerization at 6 h and induced Hmox-1 protein expression at 6 h and 24 h in HAECs. These results are consistent with the cardiovascular protective effects of coffee polyphenols and demonstrate that CGA can protect vessels and cultured endothelial cells against oxidant-induced damage. The mechanism behind the beneficial effect of CGA appears to be in part via increased production of NO and induction of Hmox-1.

Nitrate causes a dose-dependent augmentation of nitric oxide status in healthy women

Publisher: Royal Society of Chemistry (RSC)

Date: 2012

DOI: 10.1039/C2FO10206D

Abstract: Green leafy vegetables, high in dietary nitrate, may contribute to cardiovascular health by augmenting nitric oxide status. The exogenous enterosalivary pathway of nitrate reduction to nitrite appears to be a critical determinant of the effects of nitrate. Our primary objective was to investigate the dose-response of nitrate intake on nitric oxide status and nitrate reduction in the mouth. We also assessed whether antibacterial toothpaste can inhibit nitrate reduction and blunt subsequent increases in circulating nitric oxide. A randomised, controlled, crossover trial with healthy women (n = 16) was conducted. The acute effects of four doses of nitrate (0 mg, 100 mg, 200 mg, 400 mg, as well as 400 mg plus antibacterial toothpaste), administered in random order, were compared. Measurements included biomarkers of plasma nitric oxide status, assessed by measuring S-nitrosothiols + other nitroso species (RXNO) and nitrite, and a biomarker of nitrate reduction in the mouth, assessed by measuring salivary nitrite. Compared to 0 mg, all doses of nitrate resulted in higher plasma RXNO and nitrite, and salivary nitrite (P < 0.05). A linear dose-response to nitrate intake was observed with plasma RXNO and nitrite, and salivary nitrite (P 0.9) or blunt the increase in nitric oxide status (P > 0.9). Thus, our study has demonstrated that increasing nitrate intake results in a dose-related increase in nitrate reduction in the mouth and nitric oxide status, and that use of antibacterial toothpaste does not inhibit nitrate reduction or blunt increases in circulating nitric oxide.

Preoperative biomarker evaluation for the prediction of cardiovascular events after major vascular surgery

Publisher: Elsevier BV

Date: 11-2019

DOI: 10.1016/J.JVS.2019.02.041

Abstract: The cause of perioperative myocardial infarction (PMI) is postulated to involve hemodynamic stress or coronary plaque destabilization. We aimed to evaluate perioperative factors in patients with peripheral artery disease (PAD) undergoing major vascular surgery to determine the likely mechanisms and predictors of PMI. This was a prospective cohort study of 133 patients undergoing major vascular surgery including open abdominal aortic aneurysm (AAA) repair (n = 40) and major suprainguinal or infrainguinal arterial bypasses (non-AAA n = 93). Preoperative assessment with history, physical examination, and peripheral artery tonometry was performed in addition to plasma s ling of biomarkers associated with inflammation and coronary plaque instability. The primary outcome was occurrence of a 30-day cardiovascular event (CVE composite of PMI [troponin I elevation >99th percentile reference of ≥0.1 μg/L], stroke, or death). Of 133 patients, 36 patients (27%) developed a 30-day CVE after vascular surgery, and all were PMI. Patients with 30-day CVE were older (75 ± 8 years vs 69 ± 10 years, mean ± standard deviation P = .001), had higher prevalence of hypertension (94% vs 79% P = .01) and preoperative beta-blocker therapy (50% vs 29% P = .02), and had longer duration of surgery (5.1 ± 1.8 hours vs 4.0 ± 1.1 hours P < .0001). Significant elevations in cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin I, high-sensitivity troponin T, matrix metalloproteinase 3, and osteoprotegerin occurred in those who developed 30-day CVE (all P < .05). Multivariate binary logistic regression identified AAA surgery and log-transformed NT-proBNP to be independent preoperative predictors of 30-day CVE (area under the receiver operating characteristic curve = 0.81). In patients with peripheral artery disease undergoing major vascular surgery, the likely mechanism of PMI appears to be the hemodynamic stress related to the type and duration of surgery. NT-proBNP was a useful independent predictor of CVE and thus may serve as an important biomarker of cardiovascular fitness for surgery.

Quercetin and its metabolites improve vessel function by inducing eNOS activity via phosphorylation of AMPK

Publisher: Elsevier BV

Date: 10-2012

DOI: 10.1016/J.BCP.2012.07.016

Abstract: Quercetin is a major flavonoid in a wide range of fruits and vegetables. Consumption of quercetin may contribute to a reduction in risk of cardiovascular disease (CVD). Following ingestion, flavonoids are metabolized rapidly by methylation or glucuronidation, which can alter their biological activity. Certain dietary flavonoids have been shown to upregulate the expression of adenosine monophosphate-activated protein kinase (AMPK). AMPK is a conserved key enzyme in cellular energy homeostasis that affects fatty acid oxidation. The aim of the present study was to investigate the effects of supraphysiological concentrations of quercetin and its methyl and glucuronide metabolites (3'-O-methyl-quercetin and quercetin-3-O-glucuronide) on activation of AMPK and eNOS in human aortic endothelial cells (HAECs) and endothelial function in isolated aortic rings from C57BL mice. We found that 5 and 10 μM quercetin and its metabolites, and pretreatment of arteries with quercetin and its metabolites can protect vessels against hypochlorous acid-induced endothelial dysfunction in isolated arteries (P < 0.05). Inhibition of AMPK blocked these protective effects. We also found that 5 and 10 μM quercetin and its metabolites can induce activation of AMPK and eNOS in human aortic endothelial cells, and lead to an increase in the concentrations of S-nitrosothiols and nitrite in cell culture media (P < 0.05). These results provide further support for the cardioprotective effects of certain dietary flavonoids. They suggest that beneficial effects of quercetin on endothelial cell functions are in part mediated via AMPK pathway.

University Of Western Australia

Location: Australia

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Discovery Projects - Grant ID: DP1093825

Start Date: 2010

End Date: 12-2014

Amount: $288,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP110100410

Start Date: 2011

End Date: 10-2011

Amount: $173,826.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP0562463

Start Date: 11-2005

End Date: 12-2008

Amount: $195,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100125

Start Date: 06-2010

End Date: 12-2010

Amount: $330,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP0455288

Start Date: 12-2004

End Date: 12-2008

Amount: $90,168.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP0882884

Start Date: 08-2008

End Date: 12-2010

Amount: $155,200.00

Funder: Australian Research Council