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

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Modulatory Efficiency of LP/LF Nano-Combination on Neurochemical and Behavioural Retardations in the Brain of Induced-Epileptic Rats

“…In the present study, an elevation in MDA and NO content coupled with a marked drop in the activity of SOD, GPx, GSH and CAT were observed in the brain cortex and hippocampus of the SE rats, these findings agree with those previously established [24][25][26][27][28] . It was stated that the relationship between status epilepsy and ROS is well known as the epileptiform activity causes excessive free radical production of ROS, a factor believed to be involved in the mechanism leading to cell death and neurodegeneration.…”

Treatment of pilocarpine-induced epileptic seizures in adult male mice

“…In industrialized countries, epilepsy affects 40-70 people per 100,000, but in poor countries, it affects 100-190 people per 100,000 (Keykhosravi et al, 2019). When Alfred Hartmann developed phenobarbital in 1912, pharmacologic epilepsy therapy became widespread around the turn of the century (Villalba, 2017;Rostamian et al, 2021). Phenytoin, valproate, and carbamazepine were among the antiepileptic medications found during the next few decades (Wat et al, 2019).…”