The effect of neutrophil elastase inhibitor on acute tubular necrosis after renal ischemia-reperfusion injury
In renal transplantation, ischemia-reperfusion (I/R) injury is a major cause of renal dysfunction. Activated neutrophils are reported to be closely involved in I/R injury after renal transplantation. Neutrophil elastase, a protease released from activated neutrophils, damages tubular endothelial cells. We investigated the beneficial effect of neutrophil elastase inhibitor (ONO-5046.Na) on renal I/R injury in rats. The study was conducted using 10 male Lewis rats (270-320 g) that were intravenously administered ONO-5046.Na (30 mg/kg before ischemia and after reperfusion) (group A) and control rats (group B) in a 90-min renal warm I/R injury model. Neutrophil elastase expression was analyzed using immunohistochemical staining, and the degree of renal dysfunction was evaluated using H&E staining and blood biochemistry. Neutrophil elastase was detected in tubular endothelial cells. The necrotic area extended to and encompassed nearly all the ischemic kidney within 12 h after reperfusion. The necrotic area and the grade of neutrophil elastase staining were significantly reduced in group A compared to group B. Significant differences in blood urea nitrogen and serum creatinine levels were observed. Survival rates over a 14-day period were examined. No rats survived for more than 4 days in group B. However, 2 of the 10 rats (20%) in group A survived for a 14-day period. To conclude, ONO-5046.Na inhibits neutrophil elastase and reduces acute tubular necrosis. Thus, it is a potent therapeutic agent for the control of renal I/R injury in renal transplantation.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2008 |
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| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1 |
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| Enthalten in: |
Molecular medicine reports - 1(2008), 4 vom: 05. Juli, Seite 489-92 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Matsuyama, Masahide [VerfasserIn] |
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| Themen: |
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| Anmerkungen: |
Date Completed 02.10.2012 Date Revised 22.02.2013 published: Print Citation Status PubMed-not-MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM207344841 |
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| 100 | 1 | |a Matsuyama, Masahide |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The effect of neutrophil elastase inhibitor on acute tubular necrosis after renal ischemia-reperfusion injury |
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| 500 | |a Date Revised 22.02.2013 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a In renal transplantation, ischemia-reperfusion (I/R) injury is a major cause of renal dysfunction. Activated neutrophils are reported to be closely involved in I/R injury after renal transplantation. Neutrophil elastase, a protease released from activated neutrophils, damages tubular endothelial cells. We investigated the beneficial effect of neutrophil elastase inhibitor (ONO-5046.Na) on renal I/R injury in rats. The study was conducted using 10 male Lewis rats (270-320 g) that were intravenously administered ONO-5046.Na (30 mg/kg before ischemia and after reperfusion) (group A) and control rats (group B) in a 90-min renal warm I/R injury model. Neutrophil elastase expression was analyzed using immunohistochemical staining, and the degree of renal dysfunction was evaluated using H&E staining and blood biochemistry. Neutrophil elastase was detected in tubular endothelial cells. The necrotic area extended to and encompassed nearly all the ischemic kidney within 12 h after reperfusion. The necrotic area and the grade of neutrophil elastase staining were significantly reduced in group A compared to group B. Significant differences in blood urea nitrogen and serum creatinine levels were observed. Survival rates over a 14-day period were examined. No rats survived for more than 4 days in group B. However, 2 of the 10 rats (20%) in group A survived for a 14-day period. To conclude, ONO-5046.Na inhibits neutrophil elastase and reduces acute tubular necrosis. Thus, it is a potent therapeutic agent for the control of renal I/R injury in renal transplantation | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Hayama, Takuma |e verfasserin |4 aut | |
| 700 | 1 | |a Funao, Kiyoaki |e verfasserin |4 aut | |
| 700 | 1 | |a Naganuma, Toshihide |e verfasserin |4 aut | |
| 700 | 1 | |a Kawahito, Yutaka |e verfasserin |4 aut | |
| 700 | 1 | |a Sano, Hajime |e verfasserin |4 aut | |
| 700 | 1 | |a Chargui, Jamel |e verfasserin |4 aut | |
| 700 | 1 | |a Touraine, Jean-Louis |e verfasserin |4 aut | |
| 700 | 1 | |a Nakatani, Tatsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshimura, Rikio |e verfasserin |4 aut | |
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