In vivo hydroxyl radical generation in the striatum following systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice

We investigated the in vivo hydroxyl radical (OH) generation in the striatum of mice following intraperitoneal (i.p.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This resulted in a time (1.5-6.5 h) and dose dependent (0-45 mg/kg) increase in the content of 2,3-dihydroxybenzoic acid (DHBA), a reliable indicator of OH adduct of salicylate, as measured by HPLC and electrochemical detector. Severe depletion of dopamine (DA: 65%), glutathione (50%), and increase (170%) in catalase activity were observed by 7 days. The present study for the first time provides direct evidence for the generation of OH in brain following systemic administration of MPTP and suggests involvement of oxidative stress in the neurotoxic action of MPTP. (C) 2000 Elsevier Science B.V. All rights reserved.