Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy

• Published in: Free radical biology & medicine Vol. 68; pp. 260 - 267
• Main Authors: Yang, Lili, Rozenfeld, Raphael, Wu, Defeng, Devi, Lakshmi A., Zhang, Zhenfeng, Cederbaum, Arthur
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2014
• Subjects: Alcohol; Animals; Antioxidants - administration & dosage; Autophagy; Autophagy - drug effects; Binge Drinking; Cannabidiol; Cannabidiol - administration & dosage; Ethanol - toxicity; Fatty Liver - chemically induced; Fatty Liver - drug therapy; Fatty Liver - pathology; Free radicals; Hep G2 Cells; Humans; Liver - drug effects; Liver - metabolism; Liver - pathology; Mice; Oxidative stress; Oxidative Stress - drug effects; Steatosis; Oxidative stress; Alcohol; Cannabidiol; Free radicals; Autophagy; Steatosis
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2013.12.026

Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy.
•Cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms.•Cannabidiol attenuates alcohol-mediated oxidative stress.•It prevents JNK MAPK activation.•It increases autophagy.