Diallyl disulfide ameliorates ethanol-induced liver steatosis and inflammation by maintaining the fatty acid catabolism and regulating the gut-liver axis

• DOI: 10.1016/j.fct.2022.113108
• Publication Date: 2022-05-05T16:43:01Z
• Authors: Shi-Xuan Liu; Hong Liu; Shuo Wang; Cui-Li Zhang; Fang-Fang Guo; Tao Zeng
• Keywords: Inflammation; 0301 basic medicine; Ethanol; Fatty Acids; AMP-Activated Protein Kinases; 3. Good health; Allyl Compounds; Fatty Liver; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Liver; Animals; Disulfides

Diallyl disulfide (DADS) has been suggested to possess hepatoprotection against alcoholic liver disease (ALD) by a couple of pilot studies, while the underlying mechanisms remain largely unknown. This study aimed to investigate the hepatoprotective effects of DADS against ethanol-induced liver steatosis and early inflammation by using the chronic-plus-binge mice model and cultured J774A.1 macrophages and AML12 hepatocytes. We found that DADS significantly attenuated ethanol-induced elevation of serum aminotransferase activities, accumulation of liver triglyceride, hepatocytes apoptosis, oxidative stress, infiltration of macrophages and neutrophils, and proinflammatory polarization of macrophages in mice livers. In addition, chronic-plus-binge drinking induced apparent intestinal mucosa damage and disturbance of gut microbiota, endotoxemia, and activation of hepatic NF-κB signaling and NLRP3 inflammasome, which was inhibited by DADS. In vitro studies using cocultured AML12/J774A.1 cells showed that DADS suppressed ethanol/LPS-induced cell injury and inflammatory activation of macrophages. Furthermore, DADS ameliorated ethanol-induced decline of peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1 (CPT1), and phosphorylated AMP-activated protein kinase (AMPK) protein levels in mice livers and AML12 cells. These results demonstrate that DADS could prevent ethanol-induced liver steatosis and early inflammation by regulating the gut-liver axis and maintaining fatty acid catabolism.