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.
Subject(s)
Animals , Rats , Acute Kidney Injury , Apoptosis , Caspase 3 , Cell Death , Constriction , Creatinine , Cytokines , Inflammation , Kidney , Rats, Sprague-Dawley , Renal Artery , RNA, Messenger , Tumor Necrosis Factor-alphaABSTRACT
Aim To investigate the effects of Cariporide on expression of intercellular adhesion molecule-1(ICAM-1) and P-selectin and adhesion of monocytes and endothelial cells induced by lysophophatidylcholine(LPC).Methods The ratio of adhesion of monocytes and endothelial cells was assessed by measuring protein content.The expression of ICAM-1 and P-selectin in endothelial cells was examined by enzyme-linked immunosorbent assay(ELISA).Intracellular pH of endothelial cells was measured with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein(BCECF).Results The results showed that LPC enhanced the adhesion of monocytes and endothelial cells in a concentration-dependant and time-related manner.The dosage of 5,10 and 20 ?mol?L-1 Cariporide reduced the adhesive ratio of endothelial cells induced by LPC(5 mg?L-1)from 36% to 23%,18% and 16%(P
ABSTRACT
Objective To compare the cardioprotective efficacy of Cariporide as an adjunct in different pH cardioplegia. Methods Sixty-four male Sprague-Dawley rat hearts were randomly divided into 8 groups (8 rats in each group): 4 control groups and 4 treated groups with Cariporide as an adjunct to cardioplegia. After control perfusion in Langendorff mode with Krebs-Henseleit bicarbonate buffer (KHB) for 30 minutes, the isolated rat hearts were infused with different pH (pH=6.2 or 7.0 or 7.4 or 7.8, respectively) cardioplegia (without or with Cariporide) for 2 minutes to produce cardiac arrest and subjected to 60 minutes of 15?C arrest. In addition, during global ischemia, cardioplegia was reinfused for 2 minutes every 30 minutes, Sixty minutes after the ischemic arrest, cardioplegia was infused as terminal cardioplegia for 2 minutes, then the hearts were reperfused with Krebs-Henseleit bicarbonate buffer for 30 minutes. The hemodynamic parameters and the level of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) of coronary venous sinus drainage were measured before ischemia and during reperfusion. Myocardial and mitochondrial ultrastructures were observed under electronmicroscope. Results Application of Cariporide as an adjunct to cardioplegia improved significantly recovery of cardiac function and decreased the level of creatine kinase-MB(CK-MB), lactate dehydrogenase (LDH) of coronary venous sinus drainage (P