Nitric oxide: an antioxidant and neuroprotector.
Indirect evidence, including neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-neurotoxicity by nitric oxide synthase (NOS) inhibitors and resistance of transgenic animals deficient in NOS, is controversial. We have reviewed evidence in favor of oxidative stress during the development of MPTP-neurotoxicity and the influence of antioxidants, including nitric oxide (NO) and NO donors, on MPTP-induced dopaminergic neurotoxicity. Systemic administration of MPTP causes dose-dependent generation of hydroxyl radicals (OH) in vivo in the striatum in mice; OH scavengers protect dopaminergic neurons from this insult. On the other hand the role of NO in MPTP-neurotoxicity is controversial. Hitherto, no direct evidence for the involvement of NO in MPTP neurotoxicity has been available. MPTP does not affect inducible-NOS mRNA level or its expression in SN or the striatum. Nitroglycerine, a NO donor, can attenuate MPTP-induced dopamine depletion in the striatum by virtue of its OH scavenging action. Several other NO donors have also been shown to scavenge the OH generated, following Fenton chemistry in vitro, and to protect against in vivo dopaminergic neurotoxicity by small mass iron complex formation. This evidence suggests that NO renders protection against MPTP-induced OH-mediated nigrostriatal lesions, acting as an antioxidant.
Mohanakumar
Kochupurackal P
KP
Laboratory of Experimental and Clinical Neuroscience, Indian Institute of Chemical Biology, Calcutta, India. mohankumar@iicb.res.in
Thomas
Bobby
B
Sharma
Sudarshana M
SM
Muralikrishnan
Dhanasekharan
D
Chowdhury
Rukhsana
R
Chiueh
Chuang C
CC
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D019343:Citric Acid; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D020267:MPTP Poisoning / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D015259:Dopamine Agents; D005296:Ferrous Compounds; D005609:Free Radicals; D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D019343:Citric Acid; D009569:Nitric Oxide; C016600:ferrous citrate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II