Diallyl trisulfide protects against ethanol-induced oxidative stress and apoptosis via a hydrogen sulfide-mediated mechanism

• Published in: International immunopharmacology Vol. 36; pp. 23 - 30
• Main Authors: Chen, Lian-Yun, Chen, Qin, Zhu, Xiao-Jing, Kong, De-Song, Wu, Li, Shao, Jiang-juan, Zheng, Shi-Zhong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2016
• Subjects: Alcoholic fatty liver; Allium sativum; Allyl Compounds - therapeutic use; Animals; Antioxidants - therapeutic use; Apoptosis; Apoptosis - drug effects; Cell Line; Diallyl trisulfide; Ethanol; Fatty Liver, Alcoholic - drug therapy; Garlic - immunology; Hepatocytes - drug effects; Hepatocytes - pathology; Humans; Hydrogen sulfide; Male; Oxidative stress; Oxidative Stress - drug effects; Rats; Reactive Oxygen Species - metabolism; Sulfides - therapeutic use; Sulfites - metabolism; Hydrogen sulfide; Oxidative stress; Alcoholic fatty liver; Diallyl trisulfide; Apoptosis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2016.04.015

Garlic is one natural source of organic sulfur containing compounds and has shown promise in the treatment of chronic liver disease. Dietary garlic consumption is inversely correlated with the progression of alcoholic fatty liver (AFL), although the exact underlying mechanisms are not clear. Our previous studies also have shown that diallyl trisulfide (DATS), the primary organosulfur compound from Allium sativum L, displayed anti-lipid deposition and antioxidant properties in AFL. The aim of the present study was to clarify the underlying mechanisms. In the present study, we used the intragastric infusion model of alcohol administration and human normal liver cell line LO2 cultured with suitable ethanol to mimic the pathological condition of AFL. We showed that accumulation of intracellular reactive oxygen species (ROS) was lowered significantly by the administration of DATS, but antioxidant capacity was increased by DATS. Additionally, DATS inhibited hepatocyte apoptosis via down-regulating Bax expression and up-regulating Bcl-2 expression, and attenuated alcohol-induced caspase-dependent apoptosis. More importantly, using iodoacetamide (IAM) to block hydrogen sulfide (H2S) production from DATS, we noted that IAM abolished all the above effects of DATS in ethanol-treated LO2 cells. Lastly, we found DATS could increase the expressions of cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS), the major H2S-producing enzymes. These results demonstrate that DATS protect against alcohol-induced fatty liver via a H2S-mediated mechanism. Therefore, targeting H2S may play a therapeutic role for AFL. •The model of rats given a dose of ethanol mimicked human drinking habits, and it was a stable model based on the accurate dose of ethanol.•LO2 used in vitro has been widely used in studies on liver diseases.•Ethanol exposure led to reduced H2S content and DATS could enhance H2S generation in ethanol-induced fatty liver models.•DATS alleviated ethanol-induced oxidative stress and apoptosis associated with releasing of H2S.