Combined effect of sodium valproate and ascorbic acid on pentylenetetrazole-induced seizures in mice

Abstract

Epilepsy is one of the most frequent neurological afflictions characterized by excessive temporary neuronal discharges resulting in convulsion. The pathophysiology is still not fully understood. Even though oxidative stress has been implicated as one of the mechanisms, yet the management of convulsions do not take into cognizance the important role played by antioxidants. The aim of the study was to assess the combined effect of sodium valproate (conventional antiepileptic drug) and ascorbic acid (potent antioxidant) in pentylenetetrazole (PTZ) induced seizures. Thirty mice were divided into six groups of five each (n=5). Group 1 served as control and administered normal saline 1ml/kg, group 2 received sodium valproate 200mg/kg, groups 3 and 4 were administered ascorbic acid (vitamin C) 100mg/kg and 300mg/kg, groups 5 and 6 were administered ascorbic acid (vitamin C) 100mg/kg and 300mg/kg respectively, in combination with sodium valproate 200mg/kg, 15 and 30 minutes prior to intra-peritoneal injection of PTZ (65 mg/kg). Seizure latency and duration were determined. The results showed that ascorbic acid alone has no effect on the seizure parameters. Sodium valproate 200mg had protective effect on PTZ-induced seizures. Combination of 300 mg/kg ascorbic acid with 200 mg/kg sodium valproate had a significant (p<0.05) synergistic and marked protective effect, as indicated by increase in the latency of seizure and reduction in seizure duration as compared to the control. Anti-oxidant vitamin C is recommended as co-treatment with sodium valproate in the management of seizures.

Keywords: Pentylenetetrazole, sodium valproate, ascorbic acid, seizures