S-allylmercaptocysteine reduces carbon tetrachloride-induced hepatic oxidative stress and necroinflammation via nuclear factor kappa B-dependent pathways in mice

Abstract

Purpose: To study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl 4)-induced acute hepatotoxicity in the mouse model. Methods: Mice were intraperitoneally injected with CCl 4 (50 μl/kg; single dose) to induce acute hepatotoxicity with or without a 2-h pre-treatment of SAMC intraperitoneal injection (200 mg/kg; single dose). After 8 h, the blood serum and liver samples of mice were collected and subjected to measurements of histological and molecular parameters of hepatotoxicity. Results: SAMC reduced CCl 4-triggered cellular necrosis and inflammation in the liver under histological analysis. Since co-treatment of SAMC and CCl 4 enhanced the expressions of antioxidant enzymes, reduced the nitric oxide (NO)-dependent oxidative stress, and inhibited lipid peroxidation induced by CCl 4. SAMC played an essential antioxidative role during CCl 4-induced hepatotoxicity. Administration of SAMC also ameliorated hepatic inflammation induced by CCl 4 via inhibiting the activity of NF-κB subunits p50 and p65, thus reducing the expressions of pro-inflammatory cytokines, mediators, and chemo-kines, as well as promoting pro-regenerative factors at both transcriptional and translational levels. Conclusions: Our results indicate that SAMC mitigates cellular damage, oxidative stress, and inflammation in CCl4-induced acute hepatotoxicity mouse model through regulation of NF-κB. Garlic or garlic derivatives may therefore be a potential food supplement in the prevention of liver damage. © The Author(s) 2011. This article is published with open access at Springerlink.com.