Background:
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.
Methods: Based on the results, ۵۶ rats were randomly divided into seven groups of eight and treated
intraperitoneally for four weeks. Groups ۱ and ۲ received ۵۰۰ mg/kg of carbamazepine and sodium
valproate, and groups ۳, ۴, and ۵ were injected with ۲۰۰ mg/kg of phenytoin, ۲۰۰ mg/kg lamotrigine,
and ۵۰۰ 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.
Results: MDA levels in carbamazepine and phenytoin groups were significantly higher than that in
sodium valproate, lamotrigine, vigabatrin, and control groups (P < ۰.۰۵). GSH levels in carbamazepine
and phenytoin groups were meaningfully higher compared to the groups that received sodium valproate
(P < ۰.۰۵), vigabatrin, and control groups (P < ۰.۰۰۱). Based on the results, the GGT level in the
carbamazepine group was remarkably higher in comparison with the other groups (P < ۰.۰۱). ALT and
AST represented considerably higher levels in the phenytoin group compared to the vigabatrin, sodium
valproate, and control groups (P < ۰.۰۱).
Conclusion: 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.