The Role of Nitric Oxide Pathway in the Anti-Epileptogenic Effect of Valproic Acid in the Pentylenetetrazole-Kindling Model in Rats

Though valproic acid (VPA) is used to treat seizures, more investigations have been needed to understand the effect of VPA on the nitric oxide pathway in epilepsy. Our investigation aimed to study the effect of VPA on cortical and hippocampal NOS isomers in epileptogenesis processes in the PTZ kindling model of epilepsy in the rat to reveal its mechanisms of action. Twenty-four male Wistar albino rats were used in this study. The animals were divided into four groups control, PTZ without VPA, and PTZ with VPA at two doses (100 and 200 mg/kg) Rats were kindled by injections of PTZ (35 mg/kg) with drugs or vehicle 30 minutes before, once every other day for 12 times and their behavior was observed. After completing the epileptic model process, nitric oxide pathway markers (eNOS, nNOS, iNOS, and NO) in the cortex and hippocampus were assessed by using ELISA methods. VPA suppressed seizure stages and decreased nNOS, iNOS, and NO levels while increasing eNOS levels in the hippocampus and cerebral cortex. The effect of VPA on nitric oxide pathway was found to contribute to its anti-epileptic activity.