2003年3月
Apoptosis and necrosis after warm ischemia-reperfusion injury of the pig liver and their inhibition by ONO-1714
TRANSPLANTATION
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- 巻
- 75
- 号
- 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.
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
- ID情報
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- DOI : 10.1097/01.TP.0000053400.42842.5C
- ISSN : 0041-1337
- Web of Science ID : WOS:000181687600022