Dapsone prevents morphological lesions and lipid peroxidation induced by quinolinic acid in rat corpus striatum

Increasing doses of dapsone were tested on rats administered intrastriatall y with quinolinic acid in order to evaluate a possible protective action of this drug on the striatal lesions produced after the excessive activation of N-methyl-D-aspartate receptors. Morphological lesions were evaluated 7 d ays after the intrastriatal injection of quinolinate (240 nmol/mu l) by lig ht microscopy, and the ratio of neuronal damage per field was also estimate d as a quantitative index of the striatal toxicity. Quinolinate alone produ ced extensive necrosis and loss of striatal neurons. No protective effects on the striatal tissue from quinolinate-treated rats were observed at lower doses of dapsone (6.25 and 9.375 mg/kg). However, at higher doses (12.5 an d 25 mg/kg), dapsone prevented significantly the striatum from quinolinate toxicity. Dapsone alone had no effect on the striatal tissue from control r ats. A single dose of dapsone (12.5 mg/kg) was tested also on the index of lipid peroxidation 2 h after the striatal injection of quinolinate, resulti ng in a significant protection (78% vs. QUIN). Findings of this study, in a ccordance with our previous reports, demonstrate the ability of dapsone to prevent the neuronal damage associated with the excitatory action of quinol inate via overactivation of NMDA receptors, and provide evidences to suppor t the hypothesis that this drug is acting against the pattern of toxicity e licited by agonists of glutamate receptors. (C) 1999 Elsevier Science Irela nd Ltd. All rights reserved.