s-allylcysteine and Liver-Diseases--Alcoholic

Hepatocyte apoptosis is frequently observed in alcohol-related liver disease (ARLD), which ranks among the 30 leading causes of death worldwide. In the current study, we explored the impact of S-allyl-l-cysteine (SAC), an organosulfur component of garlic, on hepatocyte apoptosis induced by alcohol. Rat liver (BRL-3A) cells were challenged by ethanol with or without SAC treatment. Cell death/viability, reactive oxygen species (ROS) generation, mitochondrial Cytochrome C release, and caspase 3 activity were then examined. We found that ethanol remarkably induced apoptosis of hepatocytes, while SAC treatment rescued ethanol-induced hepatocyte injury, as demonstrated by cell counting kit-8 (CCK8) assay, TUNEL assay, and annexin V/PI staining assay. Ethanol evoked ROS generation in BRL-3A cells, and this was abated by SAC pretreatment, as indicated by 2',7'-dichlorofluorescin diacetate (DCFDA) staining assay. Moreover, ethanol suppressed cellular anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) expression, increased pro-apoptotic protein Bcl-2-associated X protein (Bax) expression, induced mitochondrial Cytochrome C release, and activated the caspase 3-dependent apoptosis pathway in BRL-3A cells. SAC was sufficient to abolish all these changes induced by ethanol, thereby revealing the molecular mechanisms underlying its protective effects. In conclusion, SAC protects hepatocytes from ethanol-induced apoptosis and may be suitable for use as a novel anti-apoptotic agent for treating ARLD.

Topics: Animals; Antioxidants; Apoptosis; Caspase 3; Cell Death; Cell Line; Cell Survival; Cysteine; Cytochromes c; Ethanol; Hepatocytes; Liver; Liver Diseases, Alcoholic; Mitochondria; Oxidative Stress; Protective Agents; Rats; Reactive Oxygen Species; Signal Transduction

In vivo protective and alleviative effects of s-allyl cysteine (SAC), s-ethyl cysteine (SEC), s-methyl cysteine (SMC), and s-propyl cysteine (SPC) against alcohol-induced hepatotoxicity in Balb/cA mice were studied. In the preventive study, SAC, SEC, SMC, or SPC, each agent at 1 g/L, was added into the drinking water for 3 wk, and the mice were then treated with ethanol to induce acute liver injury. In the alleviative study, mice were first treated by ethanol followed by the 4 agent treatments for 3 wk. The preintake of these agents significantly attenuated subsequent alcohol-induced lipid oxidation, glutathione (GSH) depletion, and activity reduction of catalase and glutathione peroxidase (P < 0.05); also attenuated were the alcohol-induced elevation of c-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor (TNF)-alpha (P < 0.05). The preintake of these agents also significantly retarded alcohol-induced cytochrome P450 2E1 (CYP2E1) activity increase (P < 0.05). In the alleviative study, posttreatments from the 4 agents restored liver GSH content (P < 0.05); however, only SEC and SPC posttreatments significantly reduced lipid oxidation and alleviated the alcohol-induced elevation of CRP, IL-6, IL-10, and TNF-alpha (P < 0.05). SEC and SPC posttreatments also significantly diminished alcohol induced CYP2E1 activity (P < 0.05). These results support that SEC and SPC could provide both preventive and alleviative effects against alcohol-induced hepatotoxicity through suppression of oxidation and inflammation.

Topics: Animals; Cysteine; Ethanol; Glutathione; Glutathione Peroxidase; Lipid Peroxidation; Liver; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred BALB C; Oxidation-Reduction; Oxidative Stress; Protective Agents; Random Allocation