Anticonvulsant and antioxidant actions of trimetazidine in pentylenetetrazole-induced kindling model in mice

Abstract

The present study was carried out to investigate the effect of trimetazidine on the course of pentylenetetrazole (PTZ)-induced chemical kindling and oxidative stress markers in PTZ-kindled mice. Kindling was induced by repeated injections of a subconvulsive dose of PTZ (30mg⁄kg, i.p.) on alternate days for 5weeks or until stage 4 of the seizure score was evoked on three consecutive administrations. Trimetazidine was administered daily in three doses (5, 10 and 20mg/kg) per orally (p.o.) along with alternate-day PTZ. Following PTZ kindling, oxidative stress parameters, i.e. levels of malondialdehyde (MDA) and reduced glutathione (GSH), were assessed in isolated homogenized whole brain tissue. The results showed that PTZ treatment progressively increased the seizure score in control mice. Biochemical analysis revealed a significant increase in MDA levels and decreased GSH levels in the brain homogenate of PTZ-kindled mice. Daily treatment with trimetazidine in doses of 10 and 20mg/kg significantly decreased the PTZ-induced seizure score. However, a low dose of trimetazidine (5mg/kg) failed to improve the seizure score. Pretreatment of trimetazidine in all doses showed an ameliorating effect on biochemical alteration induced by PTZ treatment. The results of the present study indicate the potential anticonvulsant activity of trimetazidine against PTZ-induced kindling in mice.