Manipulation of glutathione contents fails to alter dopaminergic nigrostriatal neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse

Abstract

Administration of glutathione monoethyl ester to mice increased hepatic glutathione (GSH) levels modestly, while administration of butylated hydroxyanisole increased hepatic glutathione content markedly. Yet neither substance protected mice from the toxic effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopaminergic nigrostriatal neurons, as shown by marked depletion of striatal dopamine content when animals were sacrificed. Conversely, marked lowering of GSH levels in the livers of mice by administration of buthionine sulfoximine, or in both liver and brainstem following the injection of diethyl maleate, failed to accentuate the neurotoxicity of a low dose of MPTP. Thus, although MPTP produces a drop in brainstem GSH content, this GSH deficiency may not be casually related to the neurotoxic effects of MPTP.