The possible role of endogenous glutathione as an anticonvulsant in mice

We have recently found that intracerebroventricular (i.c.v.) administration of glutathione (GSH) inhibits pentylenetetrazol-induced convulsions in mice, suggesting that GSH has an anticonvulsive action. In the present study, we investigated whether endogenous GSH play a role in regulating seizure susceptibility, using L-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis. BSO treatment (3.2 mu mol i.c.v. X 2, 48 and 24 h prior to experiments) decreased brain GSH level to 31.5% of control, and potentiated pentylenetetrazol-induced convulsions. Potentiation of convulsions by BSO treatment was recovered by supplying GSH (10 nmol, i.c.v.). These results suggest that endogenous GSH functions as an anticonvulsant. (C) 2000 Elsevier Science B.V. All rights reserved.