Nitric oxide donors protect against 1-methyl-4-phenyl pyridinium-induced experimental parkinsonism in rats: evidence for antioxida

Nitric oxide (NO) with free radical properties plays a controversial critical role under a variety of physiologic and pathologic conditions. We investigated the effects of NO donors such as S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine hydrochloride (SIN-1), sodium nitroprusside (SNP) and nitroglycerin (NG) in nigrostriatal dopaminergic toxicity caused by the potent parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+) in vivo in rats and in MPP+ induced hydroxyl radical (.OH) generation in mitochondria in vitro. NG, SNAP and SIN-1 caused significant attenuation of MPP+ induced .OH generation in mitochondria. Administration of MPP+ by intranigral infusion in rats to produce nigrostriatal damage was significantly attenuated by co-infusion of NG, SNAP and SIN-1 but not by SNP. NG, SNAP and SIN-1 exposed for 48 h to remove NO when administered similarly, failed to protect against MPP+ induced neurotoxicity in vivo. Long-term exposed SNP when administered intranigrally, caused dose-dependent depletion of striatal dopamine. These results indicate that selective NO donors can protect dopaminergic neurotoxicity caused by MPP+ by releasing NO in the nigral region and by virtue of its OH scavenging action. This study warrants the neuroprotective role of NO in dopaminergic neurodegeneration