Assessment of the biomarkers of hepatotoxicity following carbamazepine, levetiracetam, and carbamazepine-levetiracetam adjunctive treatment in male Wistar rats

Abstract

Objective: This study examined some of the biomarkers of hepatotoxicity following chronic treatment with carbamazepine (CBZ), levetiracetam (LEV), and CBZ + LEV adjunctive treatment in male rats. Method: Twenty-four male Wistar rats (140−150 g) were randomized into four groups (n = 6) to receive oral dose of normal saline (0.1 mL), CBZ (25 mg/kg), LEV (50 mg/kg) or sub-therapeutic dose of CBZ (12.5 mg/kg) together with LEV (25 mg/kg) for 28 days. Activities of the liver enzymes and oxidative stress markers were determined while liver histomorphology was also carried out. Data were analyzed using descriptive and inferential statistics. The results were presented as mean ± SEM in graphs or tables, while the level of significance was taken at p < 0.05. Results: The activities of alkaline-phosphatase and malondialdehyde concentrations increased significantly in all the drug treatment groups, while the activities of superoxide dismutase decreased significantly following CBZ, and CBZ + LEV treatment. Alanine-aminotransferase activities increased significantly in the CBZ and CBZ + LEV treated rats compared with control. The liver section of CBZ treated rats showed mild vascular congestion. Conclusion: None of these AEDs treatment is devoid of hepatotoxicity. However, the adverse effects in CBZ were greater than LEV, or CBZ + LEV adjunctive treatment.

Keywords

• Antiepileptics
• Carbamazepine
• Levetiracetam
• Carbamazepine-levetiracetam
• Hepatotoxicity