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 striatu m of mice following intraperitoneal (i.p.) administration of 1-methyl-4-phe nyl-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-dihydroxyben zoic acid (DHBA), a reliable indicator of OH adduct of salicylate, as measu red by HPLC and electrochemical detector. Severe depletion of dopamine (DA: 65%), glutathione (50%), and increase (170%) in catalase activity were obs erved by 7 days. The present study for the first time provides direct evide nce 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.