Purpose: It has been reported that nafamostat mesilate inhibits inflammatory injury via inhibition of complement activation in ischemic heart, liver, and intestine. However, it is unclear if nafamostat mesilate also inhibits apoptosis in ischemia-reperfusion (IR)einjured kidney. We therefore investigated whether nafamostat mesilate attenuates IR renal injury that involves inhibition of apoptosis. Methods. HK-2 cells and male C57BL/6 mice were used for this study. C57Bl/6 mice were divided into 4 groups: sham, nafamostat mesilate (2 mg/kg) + sham, IR injury (IR injury; reperfusion 27 minutes after clamping of both the renal artery and vein), and nafamostat mesilate + IR injury. Kidneys were harvested 24 hours after IR injury, and functional and molecular parameters were evaluated. For in vitro studies, HK-2 cells were incubated for 6 hours with mineral paraffin oil to induce hypoxic injury, and then treated with various doses of nafamostat mesilate to evaluate the anti-apoptotic effects. Results. Blood urea nitrogen, serum creatinine levels, and renal tissue injury scores in nafamostat mesilate + IR-injured mice were significantly lower than those of control IR mice (all P < .01). nafamostat mesilate significantly improved cell survival in hypoxic HK-2 cells (P < .01), significantly decreased renal Bax expression (P < .05), and increased renal Bcl-2 protein levels in IR kidneys and hypoxic HK-2 cells compared with those of the sham and control groups. The numbers of TUNEL and 8-OHDG positive cells were significantly lower in nafamostat mesilate + IR-injured kidneys compared with those in control IR-injured mice (P < .05); nafamostat mesilate treatment decreased the expression of inducible and endothelial nitric oxide synthase in IR-injured mice (P < .05). Conclusions. nafamostat mesilate ameliorates IR renal injury via inhibition of apoptosis by, at least in part, lowering nitric oxide overproduction, reducing Bax, and increasing Bcl-2.

CITATION INFORMATION: Choi D, Jeong J, Bae H, Ham Y, Lee K, Na K. Nafamostat Mesilate Ameliorates Ischemia-Reperfusion Renal Injury via Anti-Apoptotic Mechanism. Am J Transplant. 2017;17 (suppl 3).

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