title: Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin.
abstract: Peripheral neurotoxicity is one of the serious dose-limiting side effects of oxaliplatin (Oxa) when used in the treatment of malignant conditions. It is documented that it elicits major side effects specifically neurotoxicity due to oxidative stress forcing the patients to limit its clinical use in long-term treatment. Oxidative stress has been proven to be involved in Oxa-induced toxicity including neurotoxicity. The mitochondria have recently emerged as targets for anticancer drugs in various kinds of toxicity including neurotoxicity that can lead to neoplastic disease. However, there is paucity of literature involving the role of the mitochondria in mediating Oxa-induced neurotoxicity and its underlying mechanism is still debatable. The purpose of this study was to investigate the dose-dependent damage caused by Oxa on isolated brain mitochondria under in vitro conditions. The study was also designed to investigate the neuroprotective effects of nutraceuticals, curcumin (CMN), and quercetin (QR) on Oxa-induced mitochondrial oxidative stress and respiratory chain complexes in the brain of rats. Oxidative stress biomarkers, levels of nonenzymatic antioxidants, activities of enzymatic antioxidants, and mitochondrial complexes were evaluated against the neurotoxicity induced by Oxa. Pretreatment with CMN and QR significantly replenished the mitochondrial lipid peroxidation levels and protein carbonyl content induced by Oxa. CMN and QR ameliorated altered nonenzymatic and enzymatic antioxidants and complex enzymes of mitochondria. We conclude that CMN and QR, by attenuating oxidative stress as evident by mitochondrial dysfunction, hold promise as agents that can potentially reduce Oxa-induced adverse effects in the brain.
authors.affiliation: Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Waseem
authors.affiliation: Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India. drsuhelparvez@yahoo.com.
authors.forename: Suhel
authors.initials: S
authors.lastname: Parvez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003474:Curcumin / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D007700:Kinetics; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D018384:Oxidative Stress; D050050:Protein Carbonylation; D011794:Quercetin / Q000494:pharmacology*; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011794:Quercetin; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; D008995:Monoamine Oxidase; D009245:NADH Dehydrogenase; D003474:Curcumin
keywords: Anticancer drugs; Biomarkers; Mitochondrial complexes; Natural compounds; Oxidative stress