Benefical effect of neutrophil elastase inhibitor on renal warm ischemia-reperfusion injury in the rat.
Renal ischemia-reperfusion (I/R) injury is a significant problem in renal transplantation. Neutrophils play an important role in renal I/R injury. Several reports have demonstrated that neutrophil elastase derived from the activated neutrophils might play an important role in this injury. We investigated the effect of a neutrophil elastase inhibitor in renal I/R injury. Male Lewis rats (270-320 g) were used in the model. The right kidney was harvested and the left renal artery and vein were clamped at laparotomy. The kidney was reperfused after 90 minutes of ischemia. Neutrophil elastase inhibitor (ONO-5046: 30 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent neutrophil activation. In the nontreatment I/R group, no hosts survived 4 days. However, after treatment with neutrophil elastase inhibitor, 3 of 10 rats in the I/R group, survived more than 7 days. These results demonstrated that treatment with neutrophil elastase inhibitor ameliorated renal I/R injury.
Hayama
T
T
Department of Urology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Matsuyama
M
M
Funao
K
K
Tanaka
T
T
Tsuchida
K
K
Takemoto
Y
Y
Kawahito
Y
Y
Sano
H
H
Nakatani
T
T
Yoshimura
R
R
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007839:Functional Laterality; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012077:Renal Artery; D012079:Renal Circulation; D012082:Renal Veins; D015427:Reperfusion Injury / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D013449:Sulfonamides / Q000627:therapeutic use*; D016019:Survival Analysis
D004791:Enzyme Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine