Anticonvulsive and Antioxidant Effects of Pioglitazone on Pilocarpine-induced Seizures in Mice

Epilepsy is a neurological disorder caused by uncontrollable discharge of action potentials from neurons in the brain. After a seizure, oxidative stress may cause a significant neuronal damage. In the current study, we assessed the anticonvulsant and antioxidant properties of pioglitazone, a peroxisome proliferated activated receptor-γ (PPAR-γ) agonist that is used in type-2 diabetes, on pilocarpine-induced seizure in mice. 

Pilocarpine (400 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 Pilocarpine groups. After the administration of Pilocarpine all of the mice were observed for 1 hour to measure the seizure latency time. Pilocarpine-induced seizures were categorized using the Racine scale. Then all animals were decapitated, brain was removed and hippocampus was dissected. Finally, the level of Malondialdehyde (MDA) and Catalase (CAT) activity, Superoxide Dismutase (SOD), and Glutathione Reductase (GR) levels were quantified in hippocampus by biochemical methods.

Pioglitazone significantly increased the latency to seizure onset of stages 1-4 (P≤0.01-0.001). Also, pioglitazone prevented the development of stage 5 of the pilocarpine-induced seizure. After the seizure, pioglitazone significantly decreased the level of MDA (P<0.01) and elevated the levels of CAT (P<0.01), SOD (P<0.01) and GR (P<0.001) enzymes in the mice hippocampus compared to those in the pilocarpine group.

The findings of this study indicate that the antioxidant effect of pioglitazone may play an important role in its protective effects against neuronal damage caused by pilocarpine-induced seizure.