title: Sodium salicylate protects against rotenone-induced parkinsonism in rats.
abstract: Complex I deficiency culminating in oxidative stress is proposed as one of the upstream mechanisms of nigral neuronal death in Parkinson's disease. We investigated whether sodium salicylate, an active metabolite of aspirin, could afford protection against rotenone-induced oxidative stress, neuronal degeneration, and behavioral dysfunction in rats, because it has the potential to accept a molecule each of hydroxyl radical (•OH) at the third or fifth position of its benzyl ring. Rotenone caused dose-dependent increase in •OH in isolated mitochondria from the cerebral cortex and time- (24-48 h) and dose-dependent (0.1-100 µM) increase in the substantia nigra and the striatum, ipsilateral to the side of rotenone infusion. Administration of sodium salicylate at 12-h intervals for 4 days showed dose-dependent (50-100 mg/kg, i.p) reductions in the levels of •OH in the nigra on the fifth day. These animals showed significant attenuation in rotenone-induced loss in striatal dopamine levels, number of nigral dopaminergic neurons, reduced and oxidized glutathione levels, and complex I activity loss, but superoxide dismutase activity was increased further. Amphetamine- or apomorphine-induced ipsilateral rotations in rotenone-treated rats were significantly reduced in rats treated with sodium salicylate. Our results indicate a direct role of •OH in mediating nigral neuronal death by rotenone and confirm the neuroprotective potential of salicylate in a rodent model of parkinsonism.
authors: Division of Cell Biology and Physiology, Laboratory of Clinical and Experimental Neuroscience, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India. sindhu.km@uky.edu
authors: Sindhu K
authors: SK
authors: Madathil
authors: Saravanan S
authors: SS
authors: Karuppagounder
authors: Kochupurackal P
authors: KP
authors: Mohanakumar
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042967:Electron Transport Complex I / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity*; D012980:Sodium Salicylate / Q000494:pharmacology* / Q000627:therapeutic use; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014475:Uncoupling Agents / Q000633:toxicity*
chemical_list: D016861:Cyclooxygenase Inhibitors; D014475:Uncoupling Agents; D012402:Rotenone; D017665:Hydroxyl Radical; D000661:Amphetamine; D013482:Superoxide Dismutase; D042967:Electron Transport Complex I; D005978:Glutathione; D001058:Apomorphine; D004298:Dopamine; D012980:Sodium Salicylate