Trimetazidine potentiates the antiepileptic activity and ameliorates the metabolic changes associated with pentylenetetrazole kindling in rats treated with valproic acid

Oxidative stress is implicated in epileptogenesis as well as in the metabolic changes associated with increased risk of atherosclerotic vascular disease in epilepsy. The present work investigated the impact of the antioxidant trimetazidine (TMZ) on the antiepileptic activity of valproic acid (VPA) a...

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Bibliographic Details
Published in:	Canadian journal of physiology and pharmacology Vol. 95; no. 6; p. 686
Main Authors:	Sedky, Amina Ahmed, El Serafy, Osama Mahmoud Hassan, Hassan, Olfat Ahmed, Abdel-Kawy, Hala Salah, Hasanin, Amany Helmy, Raafat, Mona Hussein
Format:	Journal Article
Language:	English
Published:	Canada 01-06-2017
Subjects:	Animals Anticonvulsants - pharmacology Anticonvulsants - therapeutic use Aorta - drug effects Aorta - metabolism Aorta - pathology Biomarkers - metabolism Blood Glucose - metabolism Drug Synergism Epilepsy - drug therapy Epilepsy - metabolism Epilepsy - pathology Hippocampus - drug effects Hippocampus - metabolism Hippocampus - pathology Insulin - blood Insulin Resistance Kindling, Neurologic - drug effects Liver - drug effects Liver - metabolism Liver - pathology Male Oxidative Stress - drug effects Pentylenetetrazole - pharmacology Rats Rats, Wistar Trimetazidine - pharmacology Trimetazidine - therapeutic use Valproic Acid - pharmacology Valproic Acid - therapeutic use acide valproïque epilepsy épilepsie pentylenetetrazole valproic acid pentylènetétrazole trimetazidine trimétazidine
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Summary:	Oxidative stress is implicated in epileptogenesis as well as in the metabolic changes associated with increased risk of atherosclerotic vascular disease in epilepsy. The present work investigated the impact of the antioxidant trimetazidine (TMZ) on the antiepileptic activity of valproic acid (VPA) and on the metabolic and histological changes in hippocampal, aortic, and hepatic tissues associated with epilepsy and (or) VPA. Rats were divided into non-pentylenetetrazole (non-PTZ) group subdivided into control and VPA-treated groups, and PTZ-treated group subdivided into PTZ, PTZ/VPA, PTZ/TMZ, and PTZ/VPA + TMZ groups. VPA treatment in PTZ rats resulted in an antioxidant effect with improvement in oxidative stress, metabolic and histopathological changes induced by PTZ in hippocampus, aortic, and hepatic tissues. TMZ exhibited anticonvulsant activity and potentiated the anticonvulsant effect of VPA. Combination of TMZ with VPA induced a greater reduction in oxidative stress, improvement in the metabolic and histopathological changes compared to VPA treatment. In contrast, VPA administration in non-PTZ-treated rats induced a pro-oxidative effect, associated with metabolic and histopathological changes in aortic and hepatic tissues. These findings suggest that co-administration of TMZ with VPA in epilepsy might antagonize not only the oxidative stress associated with epilepsy but might also counteract a potential pro-oxidative effect of VPA.
ISSN:	1205-7541
DOI:	10.1139/cjpp-2016-0263