Comparison of the Hepatotoxicity of Carbamazepine, Sodium Valproate, Phenytoin, Lamotrigine, and Vigabatrin in a Rat Model

Hepatotoxicity is one of the most important side effects of anticonvulsant drugs. This study compared the hepatotoxicity of sodium valproate, carbamazepine, phenytoin, lamotrigine, and vigabatrin in male rats.

Based on the results, 56 rats were randomly divided into seven groups of eight and treated intraperitoneally for four weeks. Groups 1 and 2 received 500 mg/kg of carbamazepine and sodium valproate, and groups 3, 4, and 5 were injected with 200 mg/kg of phenytoin, 200 mg/kg lamotrigine, and 500 mg/kg vigabatrin, respectively. As control groups, the sixth and seventh received distilled water and sesame oil. Biochemical parameters such as alanine aminotransferase (ALT), aspartate transaminase (AST), and γ-glutamyl transferase (GGT) in the serum samples, as well as malondialdehyde (MDA) and glutathione (GSH) contents in liver homogenates, were measured at the end of the experiment.

MDA levels in carbamazepine and phenytoin groups were significantly higher than that in sodium valproate, lamotrigine, vigabatrin, and control groups (P<0.05). GSH levels in carbamazepine and phenytoin groups were meaningfully higher compared to the groups that received sodium valproate (P<0.05), vigabatrin, and control groups (P<0.001). Based on the results, the GGT level in the carbamazepine group was remarkably higher in comparison with the other groups (P<0.01). ALT and AST represented considerably higher levels in the phenytoin group compared to the vigabatrin, sodium valproate, and control groups (P<0.01).

Overall, carbamazepine-induced hepatotoxicity caused the most significant changes in GSH, GGT, and AST. The induction of hepatotoxicity with sodium valproate had the least effect on enzymes and was significantly different compared to carbamazepine and phenytoin groups. Because of no hepatic metabolism, the level of biomarkers did not demonstrate a considerable difference between vigabatrin and the control groups.