Expression Of Aquaporins In Rats Chronic Cyclosporine Nephrotoxicity

Objective:The present study was aimed to investigate the expression of AQP-1, AQP-2, and AQP-3in a rat model of chronic cyclosporine A (CsA) nephrotoxicity.Method:Male Sprague-Dawley rats maintained on a low salt diet were treated daily with vehicle (olive oil,1mL/kg/d, s.c.) and CsA (15mg/kg/d, s.c.) for4weeks. Body weight, water intake, urine volume, renal function, and renal histopathology (Tubulointerstitial fibrosis and apoptotic cell death) were determined. Expression of AQP-1, AQP-2, and AQP-3was studied using immunohistochemistry and immunoblotting.Results:Long-term treatment with CsA increased water intake (28.0±4.0mL vs.15.8±2mL, P<0.01) and urine volume (26±7mL vs.14±6mL, P<0.01) with the loss of body weight (328±8g vs.340±5g, P<0.01) and renal dysfunction (BUN:36±7mg/dL vs.15±4mg/dL; Scr:1.1±0.2mg/dL vs.0.8±0.1mg/dL; Ccr:0.24±0.04mL/min/100gvs.0.35±0.03mL/min/100g, P<0.01respectively) compared with control-treated rats. These functional changes were accompanied by decreases in the expression of AQP-1, AQP-3, and AQP-2in medulla, although there was no difference in AQP-2expression in the cortex. In addition, CsA treatment increased the number of TUNEL-positive cells in both the cortex and medulla. Moreover, the number of TUNEL-positive cells correlated with AQP-1, AQP-2, AQP-3expression within medulla (AQP-1:r=-0.789, P=0.001; AQP-2:r=-0.698, P=0.003; AQP-3:r=-0.515, P=0.041).Conclusion:CsA treatment impairs urine-concentrating ability by decreasing AQPs expression. Increased apoptotic cell death within medulla at least partially accounts for the CsA-induced urinary concentration defect.