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

Abstract

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.

• Authors: Shi-Xuan Liu, Hong Liu, Shuo Wang, Cui-Li Zhang, Fang-Fang Guo, Tao Zeng
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 164 Pg. 113108 (Jun 2022) ISSN: 1873-6351 [Electronic] England
• PMID: 35526736 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Allyl Compounds
• Disulfides
• Fatty Acids
• Ethanol
• diallyl disulfide
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Allyl Compounds
• Animals
• Disulfides
• Ethanol (metabolism, toxicity)
• Fatty Acids (metabolism)
• Fatty Liver (chemically induced, drug therapy, metabolism)
• Inflammation (drug therapy, metabolism)
• Liver
• Mice
• Mice, Inbred C57BL