Obata Toshio
Department of Pharmacology, Oita Medical University, 1-1, Hasama-machi, Oita 879-5593, Japan.
Toxicol Lett. 2002 Jun 14;132(2):83-93. doi: 10.1016/s0378-4274(02)00076-0.
Reactive oxygen species have been implicated in dopaminergic toxicity caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and iron. Although MPTP produces a parkinsonian syndrome after its conversion to 1-methyl-4-phenylpyridine (MPP(+)) by type B monoamine oxidase (MAO-B) in the brain, the etiology of this disease remains obscure. MPP(+) is a highly potent dopaminbergic-releasing agents and dopamine (DA) autoxidation catalyzed by iron and oxidative stress may be involved in the pathogenesis of Parkinson's disease. Neuromelanine synthesis from DA produce highly reactive free radicals. Although the controversy possible neurotoxin and/or neuroprotective roles of nitric oxide (NO) was discussed, NO contributes to oxidative injury to brain neurons in vivo. An environmental estrogen-like chemical also related to MPP(+)-induced *OH generation. This review describes actual mechanism of the free radicals formation by dialysis studies of in vivo free radical trapping in the pathogenesis of neurodegenerative disorders, including in the Parkinson's disease, Alzheimer disease and traumatic brain injuries.
活性氧与由1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和铁引起的多巴胺能毒性有关。尽管MPTP在大脑中被B型单胺氧化酶（MAO-B）转化为1-甲基-4-苯基吡啶（MPP(+)）后会产生帕金森综合征，但这种疾病的病因仍不清楚。MPP(+)是一种高效的多巴胺释放剂，铁催化的多巴胺（DA）自氧化和氧化应激可能参与帕金森病的发病机制。由DA合成的神经黑色素会产生高反应性自由基。尽管对一氧化氮（NO）可能的神经毒素和/或神经保护作用存在争议，但NO在体内会导致脑神经元的氧化损伤。一种环境雌激素样化学物质也与MPP(+)诱导的*OH生成有关。这篇综述通过对神经退行性疾病（包括帕金森病、阿尔茨海默病和创伤性脑损伤）发病机制中体内自由基捕获的透析研究，描述了自由基形成的实际机制。
