Abstract
The purpose of the present study was to investigate the effects and underlying mechanisms of diallyl sulfide (DAS), an organosulfur compound extracted from garlic, on drug-induced or chemical-induced liver injury caused by acetaminophen (APAP) or carbon tetrachloride (CCl(4)) in mice. DAS (100, 200, or 400 μmol kg(-1)) was orally administered 1 hour before APAP or CCl(4) intraperitoneal injection, and the serum and liver tissue were collected 24 hours after APAP or CCl(4) exposure. The serum aminotransferase activities and liver histopathological examination showed that DAS exhibited obvious hepatoprotective effects against acute liver injury induced by APAP or CCl(4). In addition, exposure to APAP or CCl(4) resulted in an increased content of malonaldehyde as well as a decreased ratio of reduced to oxidized glutathione, and a decreased level of superoxide dismutase and catalase activity in the liver (p < 0.05); however, pretreatment with DAS restored the perturbations of the antioxidant system in the liver. Beyond that, DAS pretreatment reduced the APAP-/CCl(4)-induced increase in phosphorylation of inhibitor of kappa B alpha (IκBα) and p65 subunit of nuclear factor kappa B (NF-κB) expression in the cytoplasm and nucleus in the liver. DAS pretreatment also decreased the excessive level of TNF-α caused by APAP or CCl(4) in serum (p < 0.05). Moreover, DAS pretreatment regulated the expression of cleaved caspase 3, Bax and Bcl-2 in the liver and suppressed APAP-/CCl(4)-induced hepatocyte apoptosis. In conclusion, DAS exhibits hepatoprotective effects against drug-induced and chemical-induced liver injuries induced by APAP or CCl(4) in mice, probably due to its ability to reduce hepatic oxidative stress and inhibit inflammatory injury and hepatocyte apoptosis.