Role of hydroxyl radical formation in neurotoxicity as revealed by in vivo free radical trapping.
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.
Obata
Toshio
T
Department of Pharmacology, Oita Medical University, 1-1, Hasama-machi, Oita 879-5593, Japan. tobata@oita-med.ac.jp
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006540:Herbicides / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D020267:MPTP Poisoning / Q000378:metabolism*; D008297:Male; D020734:Parkinsonian Disorders / Q000209:etiology
D006540:Herbicides; D017665:Hydroxyl Radical; D007501:Iron; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine