In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic neurotoxicity in the striatum

Free radical production might make a major contribution at certain stages in the progression of injury to the brain. Oxygen free radical formation has been implicated in lesions 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 dopamine (DA)-releasing agent and DA autoxidation catalyzed by iron and oxidative stress may be involved in the pathogenesis of Parkinson's disease. Histidine, a singlet oxygen (102) scavenger, protects MPP+-induced hydroxyl radical ((OH)-O-.) formation. The inhibitory effect on the susceptibility of LDL oxidation can reduce (OH)-O-. generation. These drugs may be applied as antiparkisonian agents. Further clinical investigation is necessary in future. This finding may be useful in elucidating the actual mechanism of free radical formation in the pathogenesis of neurodegenerative brain disorders, including Parkinson's disease and traumatic brain injuries.