title: Induction of a 72-kDa heat shock protein and protection against lipopolysaccharide-induced liver injury in cirrhotic rats.
abstract: OBJECTIVE
  A 70-kDa heat shock protein (stress-inducible HSP70, HSP72) has been reported to be a cytoprotectant in a variety of organs. It has been reported that HSP72 protected non-cirrhotic rats against endotoxemia. However, its cytoprotective effect against endotoxemia in cirrhotic rats has not yet been studied. In this study, we investigated the cytoprotective effect of HSP72 on lipopolysaccharide (LPS)-induced liver injury in carbon tetrachloride (CCl(4))-induced cirrhotic rats.
  
  
  METHODS
  Liver cirrhosis was produced by an 8-week intraperitoneal injection of CCl(4) in male Sprague-Dawley rats. Expression of HSP72 was investigated using western blot analysis. Cirrhotic rats were given an intraperitoneal injection of LPS (10 mg/kg) with or without hyperthermia (42.5 degrees C, 15 min) preconditioning. Liver injury was assessed biochemically (aspartate transaminase, alanine transaminase, bilirubin, lactate dehydrogenase, creatinine) and histologically. The plasma tumor necrosis factor (TNF)-alpha level was determined.
  
  
  RESULTS
  Hyperthermia preconditioning induced a 4-fold increase in HSP72 in the cirrhotic rat liver. Pre-induction of HSP72 prevented LPS-induced liver injury, as evaluated using serum biochemical parameters and histology with reduced TNF-alpha response.
  
  
  CONCLUSIONS
  These findings suggest that pre-induction of HSP72 may provide therapeutic strategies for Gram-negative sepsis-induced liver injury in liver cirrhosis.
authors.affiliation: First Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita City, Akita 910-8543, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Mikami
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Goto
authors.forename: Kouichi
authors.initials: K
authors.lastname: Miura
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Ohshima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yoneyama
authors.forename: Jiun-Guey
authors.initials: JG
authors.lastname: Lin
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.forename: Daisuke
authors.initials: D
authors.lastname: Segawa
authors.forename: Ei
authors.initials: E
authors.lastname: Kataoka
authors.forename: Masaru
authors.initials: M
authors.lastname: Odashima
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006979:Hyperthermia, Induced; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride