The Protection And The Mechanism Of S-allylcysteine On Rat With Non-alcoholic Fatty Liver Disease

Objective:To investigate the effect of S-allylcysteine (SAC), which is the one of the majorcomponent in garlic on rats with non-alcoholic fatty liver disease and its mechanism.Methods:1. The rats were divided into six groups:(1) Control group: fed normal rat chowand given a daily dose of saline solution by oral gavage;(2) HFD (high-fat diet) group:fed the HFD and given a daily dose of saline solution by oral gavage,(3) Low-doseSAC group: given the HFD and a daily dose of SAC (25mg/kg/day) by oral gavage;(4) Meduim-dose SAC group: given the HFD and a daily dose of SAC (50mg/kg/day)by oral gavage;(5) High-dose SAC group: given the HFD and a daily dose of SAC(25mg/kg/day) by oral gavage;(6) ATC (Atorvastatin calcium) group: given the HFDand a daily dose of ATC (30mg/kg/day) by oral gavage. During12weeks of HFD,the serum triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol (LDL-C) were detected usingcommercial kits by an autoanalyzer weekly in order to evaluate the model of HFD.2. In vitro antioxidant activity of SAC, DPPH and ABTS radical scavengingassay, Reducing power assay, ferrothiocyanate (FTC), and thiobarbituric acid (TBA)to evaluate the antioxidant properties of SAC.3. After12weeks, the animals were anesthetized, serum and fresh livers werecollected. TC, TG, FFA, HDL-C, and LDL-C were detected to aceess the lipidindicators. Superoxide dismutase (SOD), glutathioneperoxidase (GSH-Px),malondialdehyde (MDA), and glutathione (GSH) were measured to reflect oxidative/antioxidative status.4. The effects of SAC on the liver damagein non-alcohol fatty liver disease rats(NAFLD): AST (aspartate aminotransferase), ALT (alanine aminotransferase) activityin the serum and liver were estimated to assess the liver function. HE (hematoxylinand eosin) staining was used to analyze the extent of liver injury. The expression ofgenes related to apoptosis (caspase-3, bcl-2) in liver was assayed by immunohistochemistry and Western blot.Results:1. After12weeks of HFD and the administration of SAC, the BW in the HDFcontrol group was significantly heavier than that in the normal group (p<0.05). Aweight loss trend was observed in both the high-dose SAC with the HFD and ATCwith the HFD groups, when compared with the HFD control group, the high-doseSAC significantly reduced (p<0.01). HE staining also showed that normal groupshows normal liver histology and did not show any fat infiltration during the12weeks.The liver from HFD Group showed plenty of lipid vacuoles inside the cells. The SACor ATC groups showed showed lesser microvesicular fatty changes than the HFDgroup and excellent HFD-induced lipid accumulation alleviation. The ALT and ASTlevels were significantly decreased (p<0.05) in the SAC groups than in the HFDgroup. Compared with normal group, all lipid indicators in the HFD control grouphave a very significant increasing trend (p<0.01) except HDL-C. Compared with HFDcontrol group, SAC and ATC treatments reduced TC, TG, LDL-C and FFA in boththe serum and liver, and increased HDL-C significantly (p<0.01) compared to theHFD control group.2. During the in vitro antioxidant experiment, SAC exhibited observable stableantioxidant activity on DPPH, ABTS radical scavenging activity and Reducing power.In this study, SAC showed an excellent anti-lipid peroxidation ability, better than thepositive control Vc on β-carotene bleaching assay, FTC and TBA. During the in vivoantioxidant experiment, the SOD activity, and GSH level in both the serum and liverwere significantly lower (p<0.05) in the HFD group than in the normal group;however, the MDA level and the GSH-Px activity in the serum (p<0.05) and liver hadincreased than in the normal group. The level of the GSH and the SOD activity inboth the serum and liver were significantly increased (p<0.01) in a dose-dependentmanner in the SAC-treated group (100mg/kg) compared to the HFD group, and in theSAC-treated groups the GSH-Px activity and the MDA level was decreased in boththe serum and liver. Protein expression of cleaved caspase-3in SAC and ATC groupshad a marked reduction, and the anti-apoptosis gene bcl-2was dramatically increased. Conclusions:The results showed SAC had excellent hepatoprotective abilities on theHFD-induced NAFLD in the rats and excellent antioxidant effects in the in vitro andin vivo studies, and SAC has protective effects on liver cells because it inhibitsapoptosis, which prevents the progression of NAFLD from simple fatty liver to celldeath.