title: Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy.
abstract: 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.
authors.affiliation: School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, China. Electronic address: yangll7@mail.sysu.edu.cn.
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.affiliation: Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Rozenfeld
authors.affiliation: Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Defeng
authors.initials: D
authors.lastname: Wu
authors.affiliation: Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Lakshmi A
authors.initials: LA
authors.lastname: Devi
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China. Electronic address: zhangzhf@sysucc.org.cn.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Mount Sinai School of Medicine, New York, NY 10029, USA. Electronic address: arthur.cederbaum@mssm.edu.
authors.forename: Arthur
authors.initials: A
authors.lastname: Cederbaum
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001343:Autophagy / Q000187:drug effects; D063425:Binge Drinking; D002185:Cannabidiol / Q000008:administration & dosage*; D000431:Ethanol / Q000633:toxicity; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000975:Antioxidants; D002185:Cannabidiol; D000431:Ethanol
keywords: Alcohol; Autophagy; Cannabidiol; Free radicals; Oxidative stress; Steatosis