Melatonin and alpha lipoic acid as possible therapies for lopinavir/ritonavir-induced hepatotoxicity in albino rats

Introduction: The use of lopinavir/ritonavir (LPV/r) has decreased morbidity and mortality due to human immunodeficiency virus (HIV); however its use could be impaired by hepatotoxicity. Therefore, this study was designed to investigate the effects of melatonin (MT) and alpha lipoic acid (ALA) on LPV/r-induced hepatotoxicity in male albino rats. Methods: Rats were divided into groups and treated with MT (10 mg/kg/day), ALA (10 mg/kg/day) and LPV/r (22.9/5.71, 45.6/11.4 and 91.2/22.9 mg/kg/day) for 60 days respectively. Rats were pretreated with MT (10 mg/kg), ALA (10 mg/kg) and combined doses of ALA and MT prior to treatment with LPV/r (22.9/5.71, 45.6/11.4 and 91.2/22.9 mg/kg/day) for 60 days. Rats were sacrificed and serum was collected and evaluated for liver enzymes. The liver was harvested and evaluated for malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) levels. Results: Significant (P<0.05) decreases in baseline serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and liver MDA levels with increases in liver SOD, CAT and GSH levels were obtained in MT and ALA treated animals when compared to control. On the contrary, significant (P<0.05) and dose dependent increases in serum AST, ALT, ALP and liver MDA levels with decreases in liver SOD, CAT and GSH levels were obtained in LPV/r treated rats when compared to placebo control. However, LPV/r-induced changes in the above parameters were attenuated in MT and ALA pretreated rats. Attenuations were significantly (P<0.05) different in rats pretreated with combined doses of MT and ALA when compared to their individual doses. Conclusion: Results of this study showed that MT and ALA could be used for the treatment of LPV/r associated hepatotoxicity.