JTE-607, an inflammatory cytokine synthesis inhibitor, attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats.
Renal ischemia/reperfusion (I/R) injury is one of the main causes of postoperative renal failure. Activated neutrophils are implicated in the development of I/R-induced renal failure. JTE-607 has been reported to be a potent inhibitor of the multiple inflammatory cytokines in the endotoxic shock mouse model and heart Langendorff perfusion model. In this study, we examined whether JTE-607 attenuates I/R-induced renal injury by reducing neutrophil activation. Male wistar rats were intravenously administered JTE-607 (JTE group, 30 mg/kg) or 5% mannitol (control group) 30 min before ischemia. JTE-607 reduced the I/R-induced increases in the serum concentrations of blood urea nitrogen and creatinine, and improved the histopathologic changes, including acute tubular necrosis. I/R-induced an increase in neutrophil activation, reflected by increases in renal cytokine-induced neutrophil chemoattractant (CINC)-1 and myeloperoxidase (MPO) concentrations which were significantly reduced by JTE-607. These findings indicate that JTE-607 attenuates I/R-induced acute renal injury, probably by inhibiting neutrophil activation. JTE-607 might be a novel therapeutic strategy for the protection of postoperative renal failure in surgery associated with renal ischemia as well as renal transplantation.
Asaga
Takehiko
T
Department of Anesthesiology & Emergency Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Ueki
Masaaki
M
Chujo
Kousuke
K
Taie
Satoshi
S
D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology*; D007674:Kidney Diseases / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology*; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010879:Piperazines / Q000008:administration & dosage*; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*
D016207:Cytokines; C468268:JTE 607; D010879:Piperazines; D010649:Phenylalanine