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Nafamostat Mesilate Attenuates Ischemia-Reperfusion-Induced Renal Injury.

Abstract：

BACKGROUND:It has been reported that nafamostat mesilate (NM) inhibits inflammatory injury via inhibition of complement activation in ischemic heart, liver, and intestine. However, it is unclear if NM also inhibits apoptosis in ischemia-reperfusion (IR)-injured kidney. We therefore investigated whether NM 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, NM (2 mg/kg) + sham, IR injury (IR injury; reperfusion 27 minutes after clamping of both the renal artery and vein), and NM + 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 NM to evaluate the antiapoptotic effects. RESULTS:Blood urea nitrogen, serum creatinine levels, and renal tissue injury scores in NM + IR-injured mice were significantly lower than those of control IR mice (all P < .01). NM 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 terminal deoxynucleotide transferase-mediated dUTP nick-end labeling- and 8-oxo-2'-deoxyguanosine-positive cells were significantly lower in NM + IR-injured kidneys compared with those in control IR-injured mice (P < .05); NM treatment decreased the expression of inducible and endothelial nitric oxide synthase in IR-injured mice (P < .05). CONCLUSIONS:NM ameliorates IR renal injury via inhibition of apoptosis by, at least in part, lowering nitric oxide overproduction, reducing Bax, and increasing Bcl-2.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Na KR,Choi H,Jeong JY,Lee KW,Chang YK,Choi DE

doi

10.1016/j.transproceed.2016.03.050

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

2192-9

issue

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(16)30190-7

journal_volume

pub_type

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Nafamostat Mesilate Attenuates Ischemia-Reperfusion-Induced Renal Injury.