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Ischemic preconditioning in liver pathophysiology
Author(s) -
Arai Masahiro,
Tejima Kazuaki,
Ikeda Hitoshi,
Tomiya Tomoaki,
Yanase Mikio,
Inoue Yukiko,
Nagashima Kayo,
Nishikawa Takako,
Watanabe Naoko,
Omata Masao,
Fujiwara Kenji
Publication year - 2007
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2006.04656.x
Subject(s) - ischemic preconditioning , ischemia , medicine , kupffer cell , reperfusion injury , adenosine , liver regeneration , adenosine receptor , pharmacology , adenosine a3 receptor , anesthesia , regeneration (biology) , reactive oxygen species , receptor , microbiology and biotechnology , biology , agonist
Brief periods of tissue ischemia produced tissue resistance to prolonged ischemia and reperfusion, a phenomenon called ischemic preconditioning. The mechanisms of ischemic preconditioning were examined in a rat warm ischemia–reperfusion model as well as the effect of ischemic preconditioning on liver regeneration. Ischemic preconditioning decreased liver injury after warm ischemia–reperfusion, which was reversed by Kupffer cell depletion. Ischemic preconditioning stimulated Kupffer cells to produce reactive oxygen species. Scavengers of reactive oxygen species reversed the effect of ischemic preconditioning, and pretreatment with sublethal dose of hydrogen peroxide mimicked ischemic preconditioning effect. Rat livers were preconditioned by ischemia and subjected to 70% partial hepatectomy. Liver regeneration was then evaluated serially. Ischemic preconditioning promoted liver regeneration, which was reversed by adenosine A2 receptor antagonism and mimicked by adenosine A2 receptor agonism. Promotion of liver regeneration by ischemic preconditioning and adenosine A2 receptor agonism were reversed by Kupffer cell depletion. In conclusion, ischemic preconditioning stimulates Kupffer cells to produce reactive oxygen species, leading to hepatocyte protection against warm ischemia–reperfusion injury; and ischemic preconditioning promoted liver regeneration via adenosine A2 receptor pathway in Kupffer cells.