Depletion of glutathione in brainstem of mice caused by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is prevented by antioxidant pretreatment

C57 black mice showed significantly decreased glutathione (GSH) content in the brainstem 24 h after a single s.c. injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 40 mg/kg. This loss of GSH could be prevented by pretreating animals with large amounts of alpha-tocopherol or beta-carotene. Increasing dopamine turnover of nigrostriatal neurons in mice by dietary administration of L-dihydroxy-phenylalanine and carbidopa did not accentuate the neurotoxic effects of MPTP. It seems likely that MPTP metabolites directly damage dopaminergic nigrostriatal neurons and that GSH is consumed in attempts to detoxify these metabolites in the substantia nigra.