ORCID Profile
0000-0002-9713-1829
Current Organisations
Universidad Norbert Wiener
,
Teoma Global
,
Universidad Peruana de Ciencias Aplicadas
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Publisher: International Global Health Society
Date: 23-05-2022
Publisher: American Society of Tropical Medicine and Hygiene
Date: 07-10-2020
Publisher: Springer Science and Business Media LLC
Date: 25-12-2010
DOI: 10.1007/S00280-009-1220-5
Abstract: To evaluate, for the first time, the efficacy of copper-indomethacin in the inhibition of aberrant crypt foci formation using the azoxymethane-induced adenocarcinoma model, to examine cell viability in the HCT-116 colorectal cancer cell line, gastrointestinal permeability, mitochondrial oxidative damage, and renal toxicity in rat models. Azoxymethane-induced adenocarcinoma rats were dosed with indomethacin and copper-indomethacin for 28 days and aberrant crypt foci were evaluated. HCT-116 colorectal cancer cells were exposed to indomethacin and copper-indomethacin at 0-250 microg/mL (0-698 microM for indomethacin, and 0-147 microM for copper-indomethacin), and cell viability was measured. Acute gastrointestinal toxicity was measured using gastrointestinal permeability markers, gastrointestinal ulceration and bleeding, and measurement of an acute-phase protein haptoglobin. Effects of acute and chronic administration of indomethacin and copper-indomethacin on urinary electrolyte concentrations were examined. Both indomethacin and copper-indomethacin resulted in a significant reduction in aberrant crypt foci in azoxymethane-treated rats. In parallel, high concentrations of indomethacin and copper-indomethacin also reduced cell viability in HCT-116 colorectal cancer cells. However, copper-indomethacin was considerably safer in all measures of gastrointestinal toxicity compared to indomethacin. In addition, indomethacin reduced urinary electrolytes at an ulcerogenic dose of 10 mg/kg acutely and chronically at 3.0 mg/kg for 28 days, whereas copper-indomethacin at equimolar doses of indomethacin affected urine electrolytes after acute dosing but not after chronic dosing for 28 days. Copper-indomethacin has both gastrointestinal and renal sparing properties while maintaining efficacy in experimental adenocarcinoma.
Publisher: Informa UK Limited
Date: 29-09-2022
Publisher: Elsevier BV
Date: 05-2021
No related grants have been discovered for Dr. Jaime A. Yáñez.