Effects of diphenyl diselenide on carbon tetrachloride and diethylnitrosamine-induced hepatotoxicity in Wistar rats

Chemical/drug-induced hepatotoxicity has become one of the major concerns in medical practice. This study was designed to evaluate the possible protective effects of diphenyl diselenide (DS) against carbon tetrachloride (CCl4) and diethylnitrosamine (DEN)-induced hepatotoxicity in male Wistar rats. Forty male Wistar rats (100-120 g) were assigned into five groups of eight animals. Group 1 served as control, group 2 was given DEN (100 mg/kg) + CCl4 (0.5 ml/kg), group 3 received DEN (100 mg/kg) + CCl4 (0.5 ml/kg) + DS (5 mg/kg), group 4 received DEN (100 mg/kg)+CCl4 (0.5 ml/kg)+DS (10 mg/kg), and group 5 received DEN (100 mg/kg)+CCl4 (0.5 ml/kg)+Quercetin (QUE; 50 mg/kg). Administration of DEN and CCl4 increased the activities of serum alanine aminotransferase, myeloperoxidase, and total bilirubin level relative to controls. There were significant (p<0.05) decreases in the activities of hepatic superoxide dismutase, glutathione-s-transferase, catalase and level of total sulfhydryl by 0.72±0.03 vs 4.55±0.28, 8.8±0.74 vs 10.94±2.67, 27.17±5.49 vs 59.75±7.87 and 0.46±0.02 vs 0.60±0.01, respectively, while hepatic malondialdehyde level increased by 4.71±0.52 vs 1.68±0.43 in the [DEN+CCl4]-administered group relative to controls. The levels of TNF-ɑ and IL-1β also increased, while the BAX/BCl2 ratio decreased in the [DEN+CCl4]-administered group. Importantly, administration of DS at 10 mg/kg increased the activities of antioxidant enzymes, and BAX/BCl2 ratio and decreased the levels of inflammatory markers. Taken together, diphenyl diselenide confers protection against DEN+CCl4-induced hepatic damage via anti-oxidative and anti-inflammatory activities.