Nitric oxide - An antioxidant and neuroprotector

被引:80
作者
Mohanakumar, KP
Thomas, B
Sharma, SM
Muralikrishnan, D
Chowdhury, R
Chiueh, CC
机构
[1] Indian Inst Chem Biol, Lab Expt & Clin Neurosci, Kolkata 700032, W Bengal, India
[2] Indian Inst Chem Biol, Div Biophys, Kolkata 700032, W Bengal, India
[3] NIMH, Unit Neurotox & Neuroprotect, Clin Sci Lab, NIH, Bethesda, MD 20892 USA
来源
NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL | 2002年 / 962卷
关键词
free radical scavenger; inducible nitric oxide synthase mRNA; nitroglycerine; MPTP; hydroxyl radicals; nitric oxide donors; ferrous citrate;
D O I
10.1111/j.1749-6632.2002.tb04083.x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:389 / 401
页数:13
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