ABSTRACT
Cyclosporine A (CsA), a fungal undecapeptide, is the most common immunosuppressive drug used in organ transplantation and autoimmune diseases. However, nephrotoxicity is the major adverse effect of CsA use. The molecular mechanisms of CsA nephrotoxicity are not well characterized, but more recent studies suggest an involvement of angiotensin ll (ANG II) and reactive oxygen species in the development of cyclosporine nephrotoxicity. This study was thus designed to investigate the role of angiotensin II type I (AT1) receptor antagonist, candisartan,on CsA- induced nephrotoxicity. Three groups of rats were employed in this study; group 1 served as control, group 2 rats were treated with CsA (20mg/kg/day subcutaneously) for 21 days, and group 3 received CsA along with candisartan (1mg/kg/day perorally) 24 hr before and 21 days concurrently. Renal blood flow (RBF) was estimated by flowometer. Estimation of plasma renin activity serum creatinine, blood urea and tissue malondialdehyde content by using colorimetric methods. Renal tissue specimens were histopatholgically examined by hematoxylin & eosin staining. CsA administration for 21 days resulted in a marked renal impairment and significantly decreases (RBF), deranged the renal functions as well as renal morphology. All these factors were significantly improved by candisartan. These results clearly demonstrate the pivotal role of (AT1) receptor antagonist candisartan in CsA- induced nephrotoxicity.
Keywords: Cyclosporine, Nephrotoxicity, Candisartan, Angiotensin, Renin.