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.

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Chemotherapy-Induced Peripheral Neuropathy

“…Wassem and Parvez showed that curcumin can ameliorate changes in both enzymatic and nonenzymatic antioxidants of mitochondria in vitro. The results reveal the potential of curcumin as a substance that can diminish oxaliplatin-induced peripheral neurotoxicity [98].…”

“…Moreover, c-Fos, a marker of neuroplasticity, was decreased by rutin-or quercetinpretreatment [25]. The neuroprotective mechanism of these phytochemicals is connected to its amelioration of mitochondrial dysfunction [98]. Interestingly, quercetin, but not rutin, inhibited azoxymethane-induced colorectal carcinogenesis in rats [101].…”

Progesterone induced neuroprotection in reperfusion promoted mitochondrial dysfunction following focal cerebral ischemia in rats

“…Mitochondria of brain frontal cortex of rat were isolated by the differential centrifugation method (Waseem and Parvez, 2016). Rats were decapitated and frontal cortex were dissected and homogenized by using a mechanically driven Teflon-fitted Potter-Elvehjem type homogenizer in ice-cold buffer A.…”

“…NADH dehydrogenase activity was assayed by spectrophotometrically according to Waseem and Parvez (2016). The enzyme activity was expressed as micromoles of NADH oxidized per minute per milligram protein using a molar extinction coefficient of 21,000 M −1  cm −1 .…”

“…The activity of succinate dehydrogenase was assayed according to the method described by Waseem and Parvez (2016) by using the spectrophotometer. The enzyme activity was expressed as micromoles of succinate oxidized per minute per milligram protein using a molar extinction coefficient of 1000 M −1  cm −1 .…”