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 trans-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 trans-resveratrol (40 mg/kg i.p.) could not inhibit the convulsions though the latency was significantly increased. When multiple doses of trans-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 trans-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 trans-resveratrol-treated animals were not significantly different. The protective effect of trans-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.
Gupta
Y K
YK
Department of Pharmacology, Neuropharmacology Laboratory, All India Institute of Medical Sciences, New Delhi 110029, India. ykg@yahoo.com
Briyal
Seema
S
Chaudhary
Geeta
G
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005260:Female; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D013267:Stilbenes / Q000008:administration & dosage*
D000975:Antioxidants; D018690:Excitatory Amino Acid Agonists; D013267:Stilbenes; D008315:Malondialdehyde; D000077185:Resveratrol; D007608:Kainic Acid