Ischemic preconditioning in liver pathophysiology.
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.
Arai
Masahiro
M
Department of Gastroenterology, Toshiba General Hospital, Shinagawa-ku, Tokyo, Japan. araima-tky@umin.ac.jp
Tejima
Kazuaki
K
Ikeda
Hitoshi
H
Tomiya
Tomoaki
T
Yanase
Mikio
M
Inoue
Yukiko
Y
Nagashima
Kayo
K
Nishikawa
Takako
T
Watanabe
Naoko
N
Omata
Masao
M
Fujiwara
Kenji
K
D000818:Animals; D004195:Disease Models, Animal; D006498:Hepatectomy; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019194:Ischemic Preconditioning / Q000379:methods*; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000503:physiopathology*; D008115:Liver Regeneration; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*
D017382:Reactive Oxygen Species; D018047:Receptors, Purinergic P1; D006861:Hydrogen Peroxide