Hypothermia protects against fulminant hepatitis in mice by reducing reactive oxygen species production

Toshiharu Sakurai, Masatoshi Kudo, Tomohiro Watanabe, Katsuhiko Itoh, Hiroaki Higashitsuji, Tadaaki Arizumi, Tatsuo Inoue, Satoru Hagiwara, Kazuomi Ueshima, Naoshi Nishida, Manabu Fukumoto, Jun Fujita

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)440-446
Number of pages7
JournalDigestive Diseases
Issue number5-6
Publication statusPublished - 2013 Nov


  • Cold shock
  • Cold-inducible RNA-binding protein
  • Fulminant hepatitis
  • Hypothermia
  • Reactive oxygen species

ASJC Scopus subject areas

  • Gastroenterology


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