Evidence for hydroxyl radical scavenging action of nitric oxide donors in the protection against 1-methyl-4-phenylpyridinium-induced neurotoxicity in rats

Rebecca Banerjee, Karuppagounder S. Saravanan, Bobby Thomas, Kizhake M. Sindhu, Kochupurackal P. Mohanakumar

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)985-995
Number of pages11
JournalNeurochemical Research
Volume33
Issue number6
DOIs
Publication statusPublished - Jun 1 2008

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Keywords

  • Fenton-like reaction
  • Hemiparkinsonian animal model
  • Hydroxyl radicals
  • Mitochondria
  • Neuroprotection
  • Nitric oxide donors
  • Parkinson's disease
  • Striatum
  • Substantia nigra

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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