ENHANCEMENT OF THE ANTICONVULSANT AND NEUROPROTECTIVE EFFECTS OF SODIUM VALPROATE BY GINKGO BILOBA AGAINST KAINIC ACID-INDUCED SEIZURES IN MICE

Abstract

Sodium valproate (SVA) is a widely u sed broad spectrum antiepileptic drug. Ginkgo biloba extract (GbE- 761) is an herbal product that has promising anticonvulsant and antioxidant properties. The aim of this study is to investigate the effect of GbE-761 on the anticonvulsant and neuroprotective activity of SVA. Methods: The anticonvulsant activity of SVA (200 mg/kg, i.p.) and its combination with GbE-761, in doses 25 and 50 mg/kg, p.o. was tested against kainic acid (KA)-induced seizures in mice. The corresponding changes in brain glutamate, lipid peroxidation, glutathione (GSH) levels and glutathione peroxidase (GSH-Px) activity were in vestigated. Moreover, serum levels of neuron-specific enolase (NSA) and 8-hydroxy-2-deoxyguanosine (8-O HdG) and brain 8-OHdG level were measured. Results: Addition of GbE to SVA enhanced the anticonvulsant activity of SAV against KA-induced seizures, the fact that appeared in the form of an increase in seizure onset and decrease in percent seizures an d mortality. This effect was accompanied by a significant decrease in brain glutamate and lipid peroxidatio n and increase in brain GSH level and GSH-Px activity relative to its levels in KA-treated animals and it s levels in SVA- treated animals. In addition, serum NSE and serum and brain 8-OHdG levels significantly decreased by combined SVA and GbE treatment than its levels in animals treated with SVA alone. Conclusions: GbE- 761 enhances the anticonvulsant and neuroprotective effects of SVA againstKA-induced seizures. This effect may be mediated by multiple me chanisms that include modulation of glutamate/GAB A-ergic system, inhibition of free radical generation, scavenging of reactive oxygen species and reactivatio n of antioxidant defenses.