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Ischemic preconditioning in liver pathophysiology.

Abstract
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.
AuthorsMasahiro Arai, Kazuaki Tejima, Hitoshi Ikeda, Tomoaki Tomiya, Mikio Yanase, Yukiko Inoue, Kayo Nagashima, Takako Nishikawa, Naoko Watanabe, Masao Omata, Kenji Fujiwara
JournalJournal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 22 Suppl 1 Pg. S65-7 (Jun 2007) ISSN: 0815-9319 [Print] Australia
PMID17567470 (Publication Type: Journal Article)
Chemical References
  • Reactive Oxygen Species
  • Receptors, Purinergic P1
  • Hydrogen Peroxide
Topics
  • Animals
  • Disease Models, Animal
  • Hepatectomy
  • Hydrogen Peroxide (pharmacology)
  • Ischemic Preconditioning (methods)
  • Kupffer Cells (metabolism)
  • Liver (physiopathology)
  • Liver Regeneration
  • Rats
  • Reactive Oxygen Species (metabolism)
  • Receptors, Purinergic P1 (metabolism)
  • Reperfusion Injury (prevention & control)

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