Protective effect of trans-resveratrol against kainic acid-induced seizures and oxidative stress in rats

Overexcitation of excitatory amino acid is an important mechanism in seizure genesis wherein free radicals have recently been suggested to play a critical role. Thus, intervention by antioxidants can be a potential beneficial approach in the treatment of epilepsy. The present study was undertaken to see the effect of traps-resveratrol, a potent antioxidant, against kainic acid-induced seizures, and effect on markers of oxidative stress in brain. Kainic acid, 10 mg/kg ip, induced long-lasting seizures and associated symptoms. The brain level of malondialdehyde (MDA) was found to be significantly raised after kainic acid administration (295 +/- 18 nmol/g wet tissue) as compared to control (195 +/- 26 nmol/g wet tissue). Pretreatment (5 min) of single dose of traps-resveratrol (40 mg/kg ip) could not inhibit the convulsions though the latency was significantly increased. When multiple doses of tracts-resveratrol were injected in two-dose schedules in different animals (20 and 40 mg/kg ip, 5 min prior and repeated 30 and 90 min after kainic acid), there was significant reduction in incidence of convulsions in both treatment schedules. The brain MDA levels were found to be significantly attenuated in the traps-resveratrol-treated groups (multiple doses of 20 and 40 mg/kg) as compared to the kainic acid alone. However, the glutathione level in control, kainic acid- and traps-resveratrol-treated animals were not significantly different. The protective effect of traps-resveratrol against kainic acid-induced convulsions and the attenuation of raised MDA level suggest the potential use of antioxidants at least as adjunct therapy in epilepsy. (C) 2002 Elsevier Science Inc. All rights reserved.