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Abstract

POSSIBLE ANTICONVULSANT EFFECT OF IVABRADINE IN KAINITE –INDUCED EPILEPSY IN RATS: AMELIORATION OF OXIDATIVE STRESS

Mohamed E. Mansour and Amany N. Ibrahim*

ABSTRACT

Background: Temporal lobe epilepsy is a longer neurological disorder in which patients suffer from spontaneous seizures. New treatments with novel mechanisms of action are needed to help those patients whose seizures are resistant to available drugs. In the present study, we evaluate the possible anticonvulsant effect of ivabradine, a hyperpolarization activated cyclic nucleotide-gated channel (HCN) blocker in kainite model of temporal lobe epilepsy in rat. In addition, evaluate the oxidative stress and nitric oxide alternation Material and Methods: adult male albino rats were divided into three equal groups: control group (CN), kainic acid (KA) induced epileptic non- treated rats, epileptic rats treated with ivabradine (20mg/kg/day) one week before convulsant state with KA epileptic rats. The latency to and the duration of tonic-clonic seizures were recorded. Also, brain oxidative stress markers were measures (lipid peroxidation, and nitric oxide). Results: of the present work revealed that convulsive state induced by KA (10 mg/kg I.P) resulted in significant elevation (p≤0.05) of NOx (NO metabolites, NO2- plus NO3- as indices of NO generation), lipid peroxidation malondialdehyde in the KA–alone treated group compared with normal rats. Administration of ivabradine (20mg/kg I.P) resulted in significant reduction (P≤0.05) of duration of clonic seizures, cortical NOx and lipid peroxidation. On the other hand, ivabradine significantly increased latency of tonic-clonic seizures. Conclusion: The present data promising the anticonvulsant and potent antioxidant effects of ivabradine in epileptic animals.

Keywords: ivabradine, kainite-induced epilepsy, oxidative stress, HCN, tonic-clonic seizures.


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