The Possible Protective Role of Candesartan on Cyclosporine Induced Nephrotoxicity in Rats
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- Category: Vol. 81, March 2013
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The Possible Protective Role of Candesartan on Cyclosporine Induced Nephrotoxicity in Rats, HANAN T. EMAM, ABDELMONEM G. MADBOLY, ABEER A. SHOMAN and NOHA I. HUSSEIN
Abstract
Cyclosporine A (CsA), a fungal undecapeptide, is the most common immunosuppressive drug used in organ trans-plantation and autoimmune diseases. However, nephrotoxicity is the major adverse effect of CsA use. The molecular mech-anisms of CsA nephrotoxicity are not well characterized, but more recent studies suggest an involvement of angiotensin 11 (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, candesartan, 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 candesartan (lmg/kg/day perorally) 24 hr before and 21 days concurrently. Renal blood flow (RBF) were estimated by flowometer. Estimation of plasma renin activity, serum creatinine, blood urea and tissue malon-dialdehyde content by using colorimetric methods. Renal tissue specimens were histopatholgically examined by hema-toxylin & 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 candesartan. These results clearly demonstrate the pivotal role of AT1 receptor antagonist candesartan in CsA- induced nephrotoxicity.