Reduction in Hepatic Apoptosis Modulated by Garlic Derived S-Allylmercaptocysteine (SAMC) in Non-Alcoholic Fatty Liver Disease Rat Model Through P53-Dependent Pathways

Abstract

Purpose Previous study demonstrated that administration of garlic-derived antioxidant S-allylmercaptocysteine (SAMC) ameliorated hepatic injury in a non-alcoholic fatty liver disease (NAFLD) rat model. In the present study, we investigated the effect and mechanism of SAMC on NAFLD-induced cellular apoptosis in the liver. Methods Adult Sprague-Dawley female rats were fed with a diet comprising of highly unsaturated fat diet (30% fish oil) for 8 weeks to develop NAFLD with or without intraperitoneal injection of 200 mg/kg SAMC three times per week. After chemical euthanasia, liver samples were collected for histological, biochemical and molecular analyses. Results During NAFLD development, increased apoptotic cells were observed in the liver. Hepatic apoptosis was accompanied by activated intrinsic apoptotic pathway as shown by expressional changes of cytochrome c and Bcl-2 family genes. Extrinsic apoptotic pathway was also activated as shown by expressional changes of Fas, TRAIL, FADD and cleaved caspase-8. Increased activity of caspase-3 further confirmed the activation of apoptosis. In addition, reduced activity of LKB1/AMPK and PI3K/Akt pathways could be observed with increased expression of pro-apoptotic regulator p53 in NAFLD rats. Administration of SAMC reduced the number of apoptotic cells through down-regulation of both intrinsic and extrinsic apoptotic mechanisms. Phosphorylation status of LKB1, AMPK, PI3K, and Akt were also restored by SAMC co-treatment, leading to the reduction of p53 expression. Conclusion Administration of SAMC during NAFLD development in rats protects liver from apoptosis through p53-dependent intrinsic and extrinsic apoptotic pathways.