title: Oleanolic acid co-administration alleviates ethanol-induced hepatic injury via Nrf-2 and ethanol-metabolizing modulating in rats.
abstract: Alcoholic liver disease (ALD) is one of the leading causes of death in the world. Oxidative stress plays an important role in the pathogenesis of alcohol-induced liver injury. Our previous results have found that oleanolic acid (OA), a liver protective agent, plays a potent antioxidant activity in hepatocyte. In the present study, the protective effects of OA co-administration on ethanol-induced oxidative injury in rats were investigated through detecting hepatic histopathology, antioxidant enzymes, ethanol metabolic enzymes and inflammatory factors. Preventions of ethanol-induced oxidative injury by OA were reflected by markedly decreased serum activities of AST, ALT and significantly increased the hepatic ATP level. In addition, the increase of the hepatic TG content, MDA level and the decrease of hepatic GSH level, SOD activity, CAT activity induced by ethanol were significantly inhibited by OA co-administration. Furthermore, OA could also elevate the protein expressions and nuclear translocation of antioxidant transcription factor Nrf-2 and then up-regulated antioxidant enzymes expressions of HO-1, SOD-1 and GR. Moreover, OA co-administration can significantly reduce the activity and expressions of CYP2E1 and ADH, which has characteristic of generation ROS mediated oxidative stress and acetaldehyde respectively. Furthermore, OA co-administration could inhibition of the generation of inflammatory factors TNF-α and IL-6. Those above results indicated that OA co-administration can protect rats against ethanol-induced liver injury by induction Nrf-2 related antioxidant to maintain redox balance and modulating the ethanol-metabolizing and inflammatory pathway.
authors.affiliation: Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: liujiangzheng2@163.com.
authors.forename: Jiangzheng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, The Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: cx-hai@fmmu.edu.cn.
authors.forename: Chunxu
authors.initials: C
authors.lastname: Hai
mesh_terms: D000818:Animals; D008297:Male; D051381:Rats; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity; D008099:Liver / Q000187:drug effects; D009828:Oleanolic Acid / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood; D051267:NF-E2-Related Factor 2
chemical_list: D000431:Ethanol; D009828:Oleanolic Acid; D014280:Triglycerides; D051267:NF-E2-Related Factor 2
keywords: ALD; CYP2E1; Nrf-2; Oleanolic acid; Oxidative stress