Expression Of Erythropoietin And Its Receptor In Renal Tissues Of Rats With Chronic Cyclosporine A Nephrotoxicity

Objective:This paper examines whether cyclosporine A (CsA) treatment induces anemia and the expression of erythropoietin (EPO) and its receptor (EPOR) in chronic cyclosporine A nephrotoxicity in the rats.Methods:Sprague-Dawley rats kept on a low salt diet (0.05%sodium) were treated daily for4weeks with subcutaneous injections of vehicle (olive oil,1mL/kg) or CsA (15mg/kg). Body weight, renal function, and hematopoietic parameters were determined. In addition, renal histopathology (tubulointerstitial fibrosis), apoptotic cell death (TUNEL assay), and expressions of erythropoietin (EPO) and its receptor (EPOR) were also investigated.Results:Compared with the normal rats, rats given CsA showed loss of body weight, renal insufficiency, and anemia, with the development of striped tubulointerstitial fibrosis and apoptotic cell death. Immunohistochemistry and immunoblotting revealed that CsA treatment significantly decreased EPO expression compared with the vehicle group, whereas EPOR expression was enhanced. Furthermore, EPO protein expression was negatively associated with the number of TUNEL-positive cells and the percentage of tubulointerstitial fibrosis.Conclusion:Long-term treatment with CsA decreases intrarenal EPO expression resulting in anemia, and that this is closely related to tubular epithelial cell apoptosis.