Anticonvulsant and Antioxidant Effects of Pitavastatin Against Pentylenetetrazol-Induced Kindling in Mice.

Nastaran Faghihi,Mohammad Taghi Mohammadi

doi:10.15171/apb.2017.035

Abstract

Purpose: The pleiotropic effects of statins (antioxidant and anti-inflammation) have been reported by previous studies. Therefore, we aimed to determine whether pitavastatin has protective effects against pentylenetetrazol (PTZ)-induced kindling in mice and also whether pitavastatin improves the brain antioxidant capacity and attenuates the oxidative injuries in kindled mice. Methods: Twenty-four mice were randomly divided into four groups (each group n=6); control, PTZ-kindling and PTZ-kindled rats treated with pitavastatin (1&4 mg/kg). PTZ kindling seizures were induced by repetitive intraperitoneal injections of PTZ (65 mg/kg) every 48 hours till day twenty-one. Animals received daily oral pitavastatin for twenty-one days. Latency, score and duration of the seizures were recorded. The activities of catalase (CAT) ad superoxide dismutase (SOD), and likewise the contents of malondialdehyde (MDA) and nitrate were assessed in the brains of all rats. Results: There was a progressive reduction in latency of the kindled rats in the next injections of PTZ. Pitavastatin reduced this value (latency) particularly at higher dose. Seizures duration and score also decreased in treatment groups. SOD and CAT activities significantly decreased in PTZ-kindling group by 62% and 64%, respectively, but pitavastatin did not significantly change the SOD and CAT activities. Brain MDA and nitrate significantly increased in PTZ-kindling group by 53% and 30%, respectively. Pitavastatin at higher dose significantly decreased the MDA and nitrate contents of PTZ-kindling rats by 45% and 32%, respectively. Conclusion: Our findings revealed that pitavastatin can improve the behavioral expression of the PTZ-kindling rats and attenuate the seizure-induced oxidative/nitrosative damage.

Highlights

Epilepsy, the condition of recurrent unprovoked seizures, is one of the most common and serious brain disorders, which involves about 1% of individuals in worldwide.[1]It's characterized by abnormal hypersynchronous paroxysmal cerebral discharges from a circumscribed region or large portions of the brain.[2]
We aimed to examine the protective effects of pitavastatin in PTZ kindling model of seizure in mice
The progressive reduction of latency was observed in kindled mice treated with 1 mg/kg pitavastatin but this reduction was mild

Summary

Introduction

The condition of recurrent unprovoked seizures, is one of the most common and serious brain disorders, which involves about 1% of individuals in worldwide.[1]. It's characterized by abnormal hypersynchronous paroxysmal cerebral discharges from a circumscribed region or large portions of the brain.[2] Seizures frequently result from an imbalance of excitation and inhibition due to a failure of inhibitory neurotransmission.[3,4] The evidence linking epilepsy with dysfunction of GABAergic inhibition is substantial and GABAA receptor is a major target of antiepileptic drugs (AED).[5]. Using the drugs that impacts the ion channels of cell membranes such as GABA receptors is useful to control the seizures in approximately 70 percent of epileptic patients.[1,5] for remaining patients that have intractable seizures (30 percent) new antiepileptic drugs have slight effects.[6] new attitudes are needed to treat these patients

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