title: Neuroprotective effects of melatonin as evidenced by abrogation of oxaliplatin induced behavioral alterations, mitochondrial dysfunction and neurotoxicity in rat brain.
abstract: Neurotoxicity is a burdensome consequence of platinum-based chemotherapy that neutralizes the administration of effective dosage and often prompts treatment withdrawal. Oxaliplatin (Oxa), a third-era platinum analogue that is active against both early-organize and progressed colorectal growth, produces critical neurotoxicity. It has been reported that the Melatonin (Mel) is a pineal hormone its metabolites display important antioxidant properties in nervous system. There is dearth of literature involving the role of mitochondria and cytosolic compartments mediated Oxa-induced neurotoxicity and its underlying mechanisms are still debatable. Rats were pre-treated with Mel (10mg/kg b.wt., i.p.) and treated with Oxa (4mg/kg b.wt. i.p.) for 5 consecutive days. For neurobehavioral performances, decreased locomotor activity and muscular strength were observed in rats. Treatment with Mel in Oxa treated rats could protect the Oxa induced alterations in motor activity and muscular strength. For painful neuropathy, thermal hyperalgesia/nociceptive tests were evaluated. In addition, pre-treatment of Mel could block or alter the inactivation of Bcl-2, caspase 3 apoptotic protein and alterations Cytochrome c (Cyt c) release in an Oxa rich environment. Pre-treatment of Mel have shown an alteration in hyperalgesia behaviour in Oxa treated rats. Oxidative stress biomarkers, levels of non-enzymatic antioxidants and mitochondrial complexes were evaluated against neurotoxicity induced by Oxa. Mel pre-treatment replenished the mitochondrial lipid peroxidation levels and protein carbonyl content induced by Oxa. Mel also modulated altered non-enzymatic, enzymatic antioxidants and complex enzymes of mitochondria. Futures studies are also required to identify other molecular markers involved in neurotoxicity induced by Oxa and possible action of Mel in its modulation.
authors: Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors: Mohammad
authors: M
authors: Waseem
authors: Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
authors: Heena
authors: H
authors: Tabassum
authors: Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110 062, India. Electronic address: sparvez@jamiahamdard.ac.in.
authors: Suhel
authors: S
authors: Parvez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001927:Brain Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D008550:Melatonin
keywords: Antioxidants; Melatonin; Mitochondria; Neurotoxicity; Oxidative stress