Protective Effect of Cariporide(R) against Ischemia/Reperfusion Injury in Rat Kidney

Chae, Eun young; Choi, Bum Soon; Yang, Hyun Joo; Ahn, Kyung Ok; Yang, Chul Woo; Kim, Yong Soo; Bang, Byung Kee

Abstract

BACKGROUND
Cytoprotective effect of Na+/H+ exchanger type 1 (NHE1) inhibitors has been studied in ischemic/reperfusion (IR) injury. The aim of this study was to evaluate the renoprotective effect and the mechanism of NHE1 inhibitor (Cariporide(R)) on IR injury of rat kidney.
METHODS
IR injury was produced by clamping both renal arteries and then rats were treated with intravenous (IV) Cariporide(R) (0.5 or 1.0 mg/kg) in Sprague-Dawley rats. The effects of Cariporide(R) treatment on subsequent IR injury were evaluated in terms of renal function, tubular injury, inflammatory cytokines (IL-1beta, TNF-alpha), apoptosis, and the expression of MAPKs.
RESULTS
BUN and serum creatinine increased after IR injury compared with sham-operated controls. However, treatment with Cariporide(R) significantly reduced BUN and serum creatinine. IR injury caused severe destruction of renal tubular cells in the outer medulla, but treatment with Cariporide(R) decreased the tubular damage. Treatment with Cariporide(R) also significantly decreased the expression of IL-1beta and TNF-alpha mRNA compared with IR injury. Apoptotic cell death was increased with I/R injury, but was significantly decreased in kidneys treated with Cariporide(R). At molecular basis, caspase 3 protein decreased more in Cariporide(R)-treated group than in IR injury group. The expression of MAPKs significantly increased with IR injury compared with sham- operated controls. However, kidneys treated with Cariporide(R) showed further increase of ERK expression compared with IR injury, but showed a significant decrease of JNK expression.
CONCLUSIONS
NHE1 inhibitors, Cariporide(R), partially prevented IR injury-induced acute renal failure by the mechanism involving apoptosis, inflammation and MAPKs.