MISC

2003年3月

Apoptosis and necrosis after warm ischemia-reperfusion injury of the pig liver and their inhibition by ONO-1714

TRANSPLANTATION
  • M Meguro
  • ,
  • T Katsuramaki
  • ,
  • H Kimura
  • ,
  • M Isobe
  • ,
  • M Nagayama
  • ,
  • K Kukita
  • ,
  • A Nui
  • ,
  • K Hirata

75
5
開始ページ
703
終了ページ
710
記述言語
英語
掲載種別
DOI
10.1097/01.TP.0000053400.42842.5C
出版者・発行元
LIPPINCOTT WILLIAMS & WILKINS

Background. It is still controversial whether a major mode of cell death during hepatic ischemia-reperfusion (I/R) injuries is apoptosis or necrosis. Moreover, the correlation between these cell deaths and the effects of a novel inducible nitric oxide synthase inhibitor (ONO-1714) has not been studied before.
Methods. Pigs were subjected to 180 min of hepatic warm I/R under extracorporeal circulation. The control group was not administered ONO-1714. In the ONO-1714 group, ONO-1714 was administered 5 min before ischemia at a dose of 0.05 mg/kg through a portal vein catheter. The apoptotic and necrotic changes after reperfusion were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and hematoxylin-eosin staining. Nitrotyrosine, active caspase-3, and cytochrome c were examined by immunohistochemistry. The plasma NO2- + NO3-, aspartate aminotransferase, and lactate dehydrogenase levels were also examined.
Results. In the control group, the frequency of apoptotic cells was only 2.6%; nevertheless, that of necrotic cells was 37% at 24 hr after reperfusion. ONO-1714 significantly attenuated apoptosis and necrosis, the expression of nitrotyrosine, and the increases of the plasma aspartate aminotransferase, lactate dehydrogenase, and NO2- + NO3- levels in the reperfusion phase.
Conclusions. A major mode of cell death during hepatic warm I/R injury was necrosis, and apoptosis was not dominant. These necrotic changes were caused by the excess production of peroxynitrite, and ONO-1714 greatly attenuated I/R injuries as the result of inhibition of the peroxynitrite production.

リンク情報
DOI
https://doi.org/10.1097/01.TP.0000053400.42842.5C
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000181687600022&DestApp=WOS_CPL
ID情報
  • DOI : 10.1097/01.TP.0000053400.42842.5C
  • ISSN : 0041-1337
  • Web of Science ID : WOS:000181687600022

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