title: Hypothermia protects against fulminant hepatitis in mice by reducing reactive oxygen species production.
abstract: OBJECTIVE
  Mild hypothermia (32-33°C) shows protective effects in patients with brain damage and cardiac arrest. Although cold-inducible RNA-binding protein (CIRP) contributes to the protective effects of hypothermia through extracellular signal-regulated kinase activation in fibroblasts, the effects of hypothermia in the liver remain unclear.
  
  
  METHODS
  We analysed the effects of cold temperature on fulminant hepatitis, a potentially fatal disease, using the D-galactosamine (GalN)/lipopolysaccharide (LPS) and concanavalin (con) A-induced hepatitis models in mice. After GalN/LPS administration and anaesthesia, mice in the hypothermia group were kept at 25°C and those in control group were kept at 35°C. After concanavalin A (con A) administration, the mice in the hypothermia group were placed in a chamber with an ambient temperature of 6°C for 1.5 h.
  
  
  RESULTS
  Hypothermia attenuated liver injury and prolonged survival. Activation of c-Jun N-terminal kinase and Akt, which are involved in reactive oxygen species (ROS) accumulation, was suppressed by low temperature. Hypothermia significantly decreased oxidized protein levels, and treatment with N-acetyl-L-cysteine, an antioxidant, attenuated GalN/LPS-induced liver injury. In con A-induced hepatitis, CIRP expression was upregulated and Bid expression was downregulated, resulting in decreased apoptosis of hepatocytes in the hypothermia group.
  
  
  CONCLUSIONS
  These data suggest that hypothermia directly protects hepatocytes from cell death via reduction of ROS production in fulminant hepatitis.
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osakasayama, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Itoh
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Higashitsuji
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Arizumi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Inoue
authors.forename: Satoru
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Ueshima
authors.forename: Naoshi
authors.initials: N
authors.lastname: Nishida
authors.forename: Manabu
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Jun
authors.initials: J
authors.lastname: Fujita
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003080:Cold Temperature; D003208:Concanavalin A; D005688:Galactosamine; D006367:HeLa Cells; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007036:Hypothermia, Induced; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016601:RNA-Binding Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C106176:Cirbp protein, mouse; D008070:Lipopolysaccharides; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D005688:Galactosamine