title: Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure.
abstract: BACKGROUND
  The pathogenesis and progression of acute liver failure (ALF) are closely associated with intestinal endotoxemia because of the high permeability of the intestinal wall. Treatment with ethyl pyruvate (EP) has been shown to protect liver failure effectively. The current study aimed to explore the relationship between proinflammatory cytokines and intestinal permeability, and to investigate whether EP administration might prevent the release of multiple proinflammatory cytokines and decrease intestinal permeability and therefore, protect the liver from injury.
  
  
  METHODS
  The ALF model was induced by D-galactosamine in rats. The rats were randomly divided into control (saline, i.p.), model (D-galactosamine, 1.2 g/kg, i.p.), prevention [EP injection (40 mg/kg) 2 hours ahead of D-galactosamine] and treatment groups (EP injection 2 hours after D-galactosamine). Samples were obtained at 12 and 24 hours after ALF induction, respectively. The histology of liver and intestinal tissue was assessed. Serum alanine aminotransferase, endotoxin, D(-)-lactate, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and high mobility group box-1 (HMGB1) were evaluated. The survival of rats was also recorded.
  
  
  RESULTS
  The rats in model group showed severe damage to liver tissue and intestinal mucosa 12 and 24 hours after ALF induction. EP significantly improved liver or intestinal injury. In addition, serum endotoxin, D(-)-lactate, DAO, TNF-alpha, IFN-gamma and HMGB1 levels were significantly increased in the model group compared with the control group. There was a positive correlation between intestinal permeability and proinflammatory cytokines. EP significantly reduced serum endotoxin, D(-)-lactate, DAO, TNF-alpha, IFN-gamma and HMGB1 levels. The median survival time was significantly prolonged in both prevention and treatment groups (126 and 120 hours compared with 54 hours in the model group).
  
  
  CONCLUSIONS
  EP has protective and therapeutic effects on intestinal mucosa. EP decreases intestinal permeability, and inhibits the release of multiple proinflammatory cytokines in rats with ALF.
authors.affiliation: Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Wang
authors.forename: Lu-Wen
authors.initials: LW
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Han
authors.forename: Zuo-Jiong
authors.initials: ZJ
authors.lastname: Gong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018988:Bacterial Translocation / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D019610:Cytoprotection; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood*; D005688:Galactosamine; D018836:Inflammation Mediators / Q000097:blood*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D010539:Permeability; D011773:Pyruvates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D004731:Endotoxins; D018836:Inflammation Mediators; D011773:Pyruvates; C046522:ethyl pyruvate; D005688:Galactosamine