Ebselen blocks the quinolinic acid-induced production of thiobarbituric acid reactive species but does not prevent the behavioral alterations produced by intra-striatal quinolinic acid administration in the rat

Abstract

Ebselen (EBS) is a seleno-organic compound with glutathione peroxidase-like activity which is neuroprotective in acute stroke ischemia. In this study, we investigated the effect of EBS on quinolinic acid (QA)-induced neurotoxicity. EBS inhibited QA-induced production of thiobarbituric acid reactive species (TBARS) by striatal homogenates in vitro with an IC(50) of 1.85 microM. Intra-striatal injection of QA (360 nmol) increased striatal content of TBARS and induced convulsions and contralateral rotational behavior. Intra-striatal pre-injection of EBS (10 nmol) 15 min before QA abolished QA-induced TBARS production but did not alter QA-induced behavioral effects. The present findings suggest that EBS acts on post-receptor events, neutralizing free radicals produced by overstimulation of N-methyl-D-aspartate receptors.