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 micromol 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.
Abe
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Japan. kazuhoab@mol.f.u-tokyo.ac.jp
Nakanishi
K
K
Saito
H
H
D000818:Animals; D001921:Brain / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D003292:Convulsants; D004198:Disease Susceptibility; D004357:Drug Synergism; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000209:etiology*
D003292:Convulsants; D019328:Buthionine Sulfoximine; D005978:Glutathione; D010433:Pentylenetetrazole