Melatonin improves adriamycin-induced hepatic oxidative damage in rats

The present study investigated the possible ameliorative effects of melatonin (MLT) against adriamycin (ADR)-induced hepatotoxicity and oxidative stress in rats. The following four experimental groups were evaluated: (1) vehicle control, (2) MLT (15 mg/kg/day), (3) ADR (10 mg/kg), and (4) ADR&MLT. ADR caused severe hepatotoxicity as evidenced by an elevation of serum aspartate aminotransferase and alanine aminotransferase activities, increased total bilirubin concentration, and decreased albumin and total protein concentration, indicating hepatic function abnormalities. Histopathological examination revealed various structural changes in liver, characterized by hepatocyte degeneration/necrosis, congestion, sinusoidal dilatation, vacuolation, and inflammatory cell infiltration. The significant decrease in reduced glutathione (GSH) content, catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and the significant increase in malondialdehyde (MDA) content indicated that ADR-induced hepatotoxicity was mediated through oxidative stress. In contrast, MLT treatment significantly improved ADR-induced serum biochemical and histopathological alterations reflecting hepatic dysfunction. Moreover, MDA concentration and GSH content, GR, GPx, and SOD activities were not affected when MLT was administered in conjunction with ADR. These results indicated that MLT improved the oxidative damage induced by ADR in rat liver, presumably due to its ability to inhibit lipid peroxidation, and restore both enzymatic and nonenzymatic antioxidant activities.