Anticonvulsive and antioxidant effects of pioglitazone on pentylenetetrazol-induced seizures in mice

Introduction: Epilepsy is a neurological disorder caused by uncontrollable discharge of neurons in the brain. After a seizure oxidative stress play an important role in the oxidative neuronal damage. In this study, we evaluated the anticonvulsant and antioxidant effects of pioglitazone, a PPAR-γ agonist that is used in type2 diabetes, on pentylenetetrazol-induced seizure in mice. Methods: In this experimental studies, twenty-eight mice weighing 20-30 g were studied. Mice were divided into 4 groups including: control, pioglitazone, Pilocarpine and treatment groups. Pentylenetetrazol (85 mg/kg) or normal saline was injected intraperitoneally 4 hours after oral administration of Pioglitazone (80 mg/kg). Also carboxymethyl cellulose was administered orally in control and pentylenetetrazol groups. After the pentylenetetrazol injection all animals were observed for 1 hour to measure the seizure latency time. pentylenetetrazol-induced seizures were classified based on the Racine scale. Then all animals were decapitated, brain was removed and hippocampus was quickly dissected. Finally, the level of Malondialdehyde (MDA) and the activity of Catalase (CAT) and Superoxide dismutase (SOD) were measured in hippocampus by standard methods. Results:  Pioglitazone significantly increased the latency to seizure onset of stages 1-4 and prevented stage 5 of racin scale. After pentylenetetrazol-induced seizures, pioglitazone significantly decreased the lipid peroxidation and increased the activity of CAT and SOD enzymes in the mice hippocampus. Conclusion: The results of this study indicates that the antioxidant effect of pioglitazone may play an important role in its protective effects against neuronal damage caused by pentylenetetrazol-induced seizure.