Differential Hepatotoxic Effects of Sodium Valproate at Different Doses in Albino Rats.

ABSTRACT

Background Liver plays an essential role for transforming and clearing chemicals that may cause harmful effects to it. Sodium Valproate, renowned to be a potent antiepileptic drug, when taken in overdose may cause toxic effects to liver and other organs as well. Liver damage can be assessed with histological changes and measurement of enzymes produced by it. Objective To investigate the histological changes induced by different doses of Sodium Valproate ranging from 100-500 mg/kg/day and observe its correlation with liver enzymes level in serum. Method Three-months old albino rats were divided into six groups, five in each. Control group was treated with normal saline and rest five groups with Sodium Valproate in different doses 100, 200, 300, 400 and 500 mg/kg/day respectively. Then, liver of those experimented rats were examined histologically under the light microscope. Furthermore, Liver enzymes; Alanine Transaminase and Aspartate transaminase were measured to assess the micro-anatomical changes in liver. Result Distorted hepatic lobular architecture with aggregations of nuclei at certain interval was observed in the groups of higher doses; 300 mg/kg/day and above. However, accumulation of adipocytes was observed in all the Sodium Valproate treated rats unlike the control group. When compared the enzyme levels among the groups, it was found to be significantly increased in dose dependent manner. Besides, it also showed skin lesions in all rats treated with the dose 400 mg/kg/day and above. Conclusion Higher doses of Sodium Valproate; 300 mg/kg/day and above induces hepatotoxicity and skin lesions in adult albino rats.