Evidence for Hydroxyl Radical Scavenging Action of Nitric Oxide Donors in the Protection Against 1-Methyl-4-phenylpyridinium-induced Neurotoxicity in Rats |
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Authors: | Rebecca Banerjee Karuppagounder S. Saravanan Bobby Thomas Kizhake M. Sindhu Kochupurackal P. Mohanakumar |
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Affiliation: | (1) Division of Cell Biology & Physiology, Laboratory of Clinical and Experimental Neuroscience, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata, 700 032, India;(2) Present address: Department of Neurology and Neuroscience, Burke Rehabilitation Hospital, White Plains, NY 10605, USA;(3) Present address: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, A-501, New York, NY 10021, USA |
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Abstract: | In the present study we provide evidence for hydroxyl radical (•OH) scavenging action of nitric oxide (NO•), and subsequent dopaminergic neuroprotection in a hemiparkinsonian rat model. Reactive oxygen species are strongly implicated in the nigrostriatal dopaminergic neurotoxicity caused by the parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). Since the role of this free radical as a neurotoxicant or neuroprotectant is debatable, we investigated the effects of some of the NO• donors such as S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine hydrochloride (SIN-1), sodium nitroprusside (SNP) and nitroglycerin (NG) on in vitro •OH generation in a Fenton-like reaction involving ferrous citrate, as well as in MPP+-induced •OH production in the mitochondria. We also tested whether co-administration of NO• donor and MPP+ could protect against MPP+-induced dopaminergic neurotoxicity in rats. While NG, SNAP and SIN-1 attenuated MPP+-induced •OH generation in the mitochondria, and in a Fenton-like reaction, SNP caused up to 18-fold increase in •OH production in the latter reaction. Striatal dopaminergic depletion following intranigral infusion of MPP+ in rats was significantly attenuated by NG, SNAP and SIN-1, but not by SNP. Solutions of NG, SNAP and SIN-1, exposed to air for 48 h to remove NO•, when administered similarly failed to attenuate MPP+-induced neurotoxicity in vivo. Conversely, long-time air-exposed SNP solution when administered in rats intranigrally, caused a dose-dependent depletion of the striatal dopamine. These results confirm the involvement of •OH in the nigrostriatal degeneration caused by MPP+, indicate the •OH scavenging ability of NO•, and demonstrate protection by NO• donors against MPP+-induced dopaminergic neurotoxicity in rats. |
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Keywords: | Nitric oxide donors Neuroprotection Hydroxyl radicals Parkinson’ s disease Substantia nigra Striatum Mitochondria Fenton-like reaction Hemiparkinsonian animal model |
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