Anticonvulsive and Antioxidant Effects of Pioglitazone on Pentylenetetrazole-induced Seizures in Rats

Background: Epilepsy is a neurologic dysfunction caused by abnormal electrical activity in the brain. Oxidative stress is involved in the seizure-induced brain damage.  Objective: This study aimed to evaluate the anticonvulsant and antioxidant effects of pioglitazone (a peroxisome proliferator-activated receptor gamma agonist used for treatment of type 2 diabetes) on Pentylenetetrazole (PTZ)-induced seizure in rats.  Methods: In this experimental study, 28 rats weighing 20-30 g were divided into four groups of control, pioglitazone, PTZ, and treatment. For treatment, PTZ (85 mg/kg) or normal saline was injected intraperitoneally and 4 hours later, pioglitazone (80 mg/kg) was administrated orally. Carboxymethylcellulose was administered orally in the control and PTZ groups, instead of pioglitazone. One hour after PTZ injection, seizure severity was assessed using Racine scale. Then, the rats were decapitated and the Malondialdehyde (MDA) level and the activity of Catalase (CAT) and Superoxide Dismutase (SOD) in their hippocampus samples were measured by standard methods. Findings: Pioglitazone administration significantly increased the latency to the onset of seizure stages 1-4 and prevented the stage 5. It significantly reduced the lipid peroxidation caused by PTZ-induced seizure and increased the activity of CAT and SOD enzymes in the hippocampus of rats.  Conclusion: Antioxidant effects of pioglitazone may play a role in preventing stable PTZ-induced seizures and protecting neurons from seizure-caused damage.