Evidence for Hydroxyl Radical Scavenging Action of Nitric Oxide Donors in the Protection Against 1-Methyl-4-phenylpyridinium-induced Neurotoxicity in Rats

    loading  Checking for direct PDF access through Ovid


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.

Related Topics

    loading  Loading Related Articles