title: Protective effect of hyperoside against acetaminophen (APAP) induced liver injury through enhancement of APAP clearance.
abstract: Acetaminphen (APAP) overdose leads to severe hepatotoxicity. Apocynum venetum L. (A. venetum) possess potent hepatoprotective effect. Hyperoside is one of the major compounds exist in Apocynum venetum L. and might be a potential agent to protect against APAP-induce liver injury. In this study, we investigated the effect of hyperoside on APAP hepatotoxicity in mice. Mice were treated intragastrically with hyperoside (10, 50 or 100 mg/kg) for 3 days before APAP (300 mg/kg) injection. APAP alone caused severe liver injury characterized by significantly increased serum aminotransferase levels, hepatic malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) formation, as well as liver superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) depletions. Hyperoside significantly attenuated APAP-induced liver damages in a dose dependent manner, and 100 mg/kg was the most effective dose. Further study confirmed that hyperoside was able to increase activities and mRNA expressions of uridine diphoshate glucuronosyltransferases (UGTs) and sulfotransferases (SULTs), as well as to inhibit CYP2E1 activities, and thereby suppressed toxic intermediate formation and promoted APAP hepatic detoxification. Nrf-2 activation might be involved in hyperoside induced up-regulation of phase II enzymes. Collectively, our data provide evidence that hyperoside protected the liver against APAP induced injury mainly by accelerating APAP harmless metabolism, implying that hyperoside can be considered as a potential natural hepatoprotective agent.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China; Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin, Germany.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Xie
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China; College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China. Electronic address: zhang.xy@nwsuaf.edu.cn.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China; Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin, Germany.
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Melzig
mesh_terms: D000082:Acetaminophen / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D062787:Drug Overdose / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger; C002744:3-nitrotyrosine; D000082:Acetaminophen; D014443:Tyrosine; C021304:hyperoside; D011794:Quercetin; D019392:Cytochrome P-450 CYP2E1; D014453:Glucuronosyltransferase; D015238:Sulfotransferases
keywords: Acetaminophen (APAP); Hepatic detoxification; Hyperoside; Sulfotransferases (SULTs); Uridine diphoshate glucuronosyltransferases (UGTs)