GM1 ganglioside attenuates convulsions and thiobarbituric acid reactive substances production induced by the intrastriatal injection of methylmalonic acid

Abstract

The effects of the administration of monosialoganglioside (GM1) on methylmalonic acid (MMA)-induced convulsions, production of thiobarbituric acid reactive substances (TBARS) and on the striatal content of ascorbic acid and total non-protein thiol (SH) groups were evaluated in adult male rats. Animals received two intraperitoneal injections of GM1 (50 mg/kg) or saline (0.85% NaCl) spaced 24 h apart. Thirty minutes after the second GM1 or saline injection, L-MMA (6 mumol) or NaCl (9 mumol) was injected into the right striatum and the animals were observed for the appearance of convulsions for 15 min. the animals were sacrificed and their striatal content of ascorbic acid, SH groups and TBARS was measured. the effect of GM1 on MMA-induced TBARS production in striatal homogenates was also evaluated in vitro.MMA injection caused convulsions (Sal-MMA: 9.8 +/- 1.4 episodes, which lasted 271 +/- 48 s) and increased the striatal content of TBARS (Sal-MMA: 149.0 +/- 11.5 nmol MDA/g tissue), but did not alter total striatal SH or ascorbic acid contents. GM1 pretreatment decreased MMA-induced convulsions (GM1-MMA: 6.3 +/- 2.0 episodes, which lasted 115.1 +/- 42.2 s) and TBARS increase (GM1-MMA: 102.4 +/- 19.5 nmol MDA/g tissue). GM1 pretreatment increased ascorbic acid content of the striata (saline-pretreated: 1514 +/- 75.9; GM1-pretreated: 1878.6 +/- 102.8 mug ascorbic acid/mg tissue). MMA increased TBARS production in vitro, and GM1 had no effect on such MMA-induced effect.This study provides evidence that GM1 increases striatal ascorbic acid content and decreases MMA-induced neurotoxicity assessed by behavioral and neurochemical parameters. (C) 2003 Elsevier B.V. All rights reserved.