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

Saba Rostamian,Samaneh Keshavarz Hedayati,Ehsan Aali,Sara Khosraviani,Yazdan Naderi

doi:10.32598/ijt.15.4.833.1

Saba Rostamian, Samaneh Keshavarz Hedayati + Show 3 more

Open Access

https://doi.org/10.32598/ijt.15.4.833.1

Copy DOI

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.

Highlights

E pilepsy is a chronic disorder of the Central Nervous System (CNS) that is associated with relapsing seizures [1]
Effect of pioglitazone on convulsion: The results indicated that the administration of pioglitazone (80mg/kg, PO) or its vehicle did not induce seizure in the mice
Comparisons between the pioglitazone and pilocarpine groups indicated that the pioglitazone administration, four hours before injecting pilocarpine, significantly increased the onset of stages 1 to 4 of seizure (P≤0.01-0.001)

Summary

Introduction

E pilepsy is a chronic disorder of the Central Nervous System (CNS) that is associated with relapsing seizures [1]. Over 60% of people with epilepsy need anticonvulant medications [5]. These drugs have side effects, such as drowsiness, ataxia and cognitive disorders [6, 7]. There is a need for the development of new anticonvulsant medications with low side effects and high efficacy [5, 6]. Clinical trials have shown that adding antioxidants, such as melatonin, to antiepileptic drugs reduces neurological disorders caused by epilepsy [9]. Epilepsy is a neurological disorder caused by uncontrollable discharge of action potentials from neurons in the brain. 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

Results

Conclusion