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) 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.
a Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Amina Ahmed
AA
Sedky
a Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Osama Mahmoud Hassan
OMH
El Serafy
a Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Olfat Ahmed
OA
Hassan
a Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Hala Salah
HS
Abdel-Kawy
a Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Amany Helmy
AH
Hasanin
b Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Mona Hussein
MH
Raafat
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D004357:Drug Synergism; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007696:Kindling, Neurologic / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014292:Trimetazidine / Q000494:pharmacology* / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D014635:Valproic Acid; D014292:Trimetazidine; D010433:Pentylenetetrazole
acide valproïque; epilepsy; pentylenetetrazole; pentylènetétrazole; trimetazidine; trimétazidine; valproic acid; épilepsie