title: Sodium butyrate protects against toxin-induced acute liver failure in rats.
abstract: BACKGROUND
  Acute liver failure (ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats.
  
  
  METHODS
  All rats were randomly divided into control, model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+ D-galactosamine+lipopolysaccharide. After induction of ALF, the rats in the treatment group received sodium butyrate (500 mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1 (HMGB1), liver function parameters, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were measured. The expression of HMGB1 and nuclear factor-kappa B (NF-kappaB) p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed.
  
  
  RESULTS
  Serum endotoxin, alanine aminotransferase, HMGB1, TNF-alpha and IFN-gamma were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group (P<0.05). Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-kappaB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF (P<0.05).
  
  
  CONCLUSIONS
  Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.
authors.affiliation: Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China. zjgong@163.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.forename: Lu-Wen
authors.initials: LW
authors.lastname: Wang
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Han
authors.forename: Zuo-Jiong
authors.initials: ZJ
authors.lastname: Gong
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D020148:Butyric Acid / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D004195:Disease Models, Animal; D005688:Galactosamine; D024243:HMGB1 Protein / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D010539:Permeability; D020011:Protective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C422455:ALB protein, human; D015415:Biomarkers; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D020011:Protective Agents; C498145:Rela protein, rat; D012709:Serum Albumin; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D020148:Butyric Acid; D005688:Galactosamine; D007371:Interferon-gamma; D000075462:Serum Albumin, Human