Effect of specific neutrophil elastase inhibitor on ischemia/reperfusion injury in rat liver transplantation

Yuji Soejima, Katsuhiko Yanaga, Takashi Nishizaki, Tomoharu Yoshizumi, Hideaki Uchiyama, Keizo Sugimachi

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Activated neutrophils have been implicated as playing an important role in ischemia/reperfusion injury of the liver by releasing toxic mediators such as oxygen free radicals and elastases. In the present study, we evaluated the effect of a novel, specific neutrophil elastase inhibitor (ONO-5046) on cold- ischemia/reperfusion injury of the liver allograft in rodents. Livers from male Lewis rats were procured and stored cold (4°C) in lactated Ringer's solution and transplanted orthotopically. Recipients were divided into three groups: Vehicle group, 5-h preservation and vehicle (n = 8); ONO-5046 group, 5-h preservation and administration of ONO-5046 (n = 8); and Control group, minimum preservation only (n = 8). Bile output after reperfusion was significantly larger in the ONO5046 group compared to the Vehicle group (P < 0.05 or less). Sinusoidal endothelial cell function represented by the serum hyaluronic acid concentration at 120 min after reperfusion of the ONO-5046 group was significantly lower than that in the Vehicle group (17.0 ± 7.9 vs 36.2 ± 14.9 ng/ml, P < 0.05), whereas serum transaminase levels 120 min after reperfusion were comparable between the two groups. Liver tissue energy charge 120 min after reperfusion was significantly better in the ONO-5046 group compared to the Vehicle group (P < 0.05). Furthermore, the number of neutrophils infiltrating the allograft after reperfusion was significantly depressed in the ONO-5046 group compared to the Vehicle group (P < 0.02). These data suggest that the neutrophil elastase might cause liver damage early after reperfusion in cold-stored liver, which can be ameliorated by the administration of a specific neutrophil elastase inhibitor, ONO-5046.

Original languageEnglish
Pages (from-to)150-154
Number of pages5
JournalJournal of Surgical Research
Volume86
Issue number1
DOIs
Publication statusPublished - Sep 1999

All Science Journal Classification (ASJC) codes

  • Surgery

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