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The effect of antagonism of adenosine A1 receptor against ischemia and reperfusion injury of the liver

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Title: The effect of antagonism of adenosine A1 receptor against ischemia and reperfusion injury of the liver
Authors: Magata, Shinichiro Browse this author
Taniguchi, Masahiko Browse this author
Suzuki, Tomomi Browse this author
Shimamura, Tsuyoshi Browse this author
Fukai, Moto Browse this author
Furukawa, Hiroyuki Browse this author
Fujita, Miri Browse this author
Todo, Satoru Browse this author →KAKEN DB
Keywords: liver
ischemia and reperfusion injury
adenosine A1 receptor antagonist
Issue Date: 1-May-2007
Publisher: Elsevier
Journal Title: Journal of Surgical Research
Volume: 139
Issue: 1
Start Page: 7
End Page: 14
Publisher DOI: 10.1016/j.jss.2006.09.021
PMID: 17336335
Abstract: Background: Adenosine is known to exert protective roles in hepatic ischemia and reperfusion injury, while all adenosine receptors do not play the cytoprotective roles. We have tested our hypothesis that blockage of adenosine binding to A1 receptor by its antagonist, KW3902 [8-(noradamantan-3-yl)-1,3-dipropylxanthine] attenuates hepatic ischemia-reperfusion injury. Methods: Adult female beagle dogs underwent a 2 h total hepatic vascular exclusion (THVE) with a venovenous bypass. Nontreated animals that underwent THVE with a venovenous bypass alone were used as the control (Group CT, n = 6). KW3902 was given to the animals by continuous intraportal infusion for 60 min before ischemia at a dose of 1μg/kg/min (Group KW, n = 6). Two wk survival, hemodynamics, hepatic tissue blood flow (HTBF), liver function, energy metabolism, cAMP concentration, and histopathological findings were studied. Results: Two wk animal survival was significantly improved in group KW compared with that in group CT (group CT: 16.7% versus group KW: 83.3%). HTBF, liver function, and hepatic adenine nucleotide concentration were remarkably better in group KW than group CT. In addition, cAMP concentration in group KW was maintained significantly higher than group CT. Histopathological examination revealed preservation of hepatic architecture and suppression of neutrophil infiltration into hepatic tissue in group KW. Conclusion: Administration of adenosine A1 receptor antagonist before ischemia attenuates hepatic ischemia-reperfusion injury. To elicit the beneficial effect of adenosine against ischemia and reperfusion injury of the liver, it is important to oppose adenosine A1 receptor activation.
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 藤堂 省

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