title: Hepatoprotective effect of isoquercitrin against acetaminophen-induced liver injury.
abstract: OBJECTIVE
  Acetaminophen (APAP) overdose leads to severe hepatotoxicity. Isoquercitrin exhibited potential hepatoprotective effect in our previous study. The present investigation aimed to evaluate the effect of isoquercitrin against APAP induced liver injury and to explore its possible mechanism.
  
  
  METHODS
  Mice were treated intragastrically with isoquercitrin (10, 20, or 50mg/kg) for 3days before APAP (300mg/kg) injection. After 24h from APAP treatment, the levels of serum aminotransferase, hepatic oxidative stress and nitrosative stress biomarkers were determined by commercial kits or western bolt. Activities of UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs) and cytochrome 2E1 (CYP2E1) were evaluated using ELISA methods and standard biochemical procedures. Subsequently, the protein and mRNA levels of inflammatory factors including TNF-α, IL-1β, IL-6 and iNOS were determined using ELISA methods, western blot or real-time PCR. The effect of isoquercitrin on APAP activated NFκB/MAPK pathway was assessed by western bolt.
  
  
  RESULTS
  Isoquercitrin pretreatments markedly attenuated APAP induced hepatic oxidative stress, nitrosative stress and centrilobular necrosis. In addition to potent antioxidant activity, isoquercitrin was able to regulate the activities of SULTs and CYP2E1, therefore promoted APAP hepatic detoxification. The anti-inflammatory activity of isoquercitrin which involved in the amelioration of iNOS, TNF-α, IL-1β and IL-6 production via the blockade of NF-κB and MAPK pathways also responsible for its hepatoprotective effect.
  
  
  CONCLUSIONS
  Our data evidenced that isoquercitrin protected liver from APAP induced injury though inhibition of oxidative stress, nitrosative stress and inflammation, as well as regulation of APAP metabolism, suggesting that isoquercitrin could be a potential hepatoprotective agent.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, 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: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, 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 / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D010851:Picrates / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D010851:Picrates; D020011:Protective Agents; D012333:RNA, Messenger; C016527:isoquercitrin; D000082:Acetaminophen; D011794:Quercetin; C004931:1,1-diphenyl-2-picrylhydrazyl; D020928:Mitogen-Activated Protein Kinases
keywords: Acetaminophen; Anti-inflammatory; Anti-oxidative; CYP2E1; Isoquercitrin; SULTs