Cyclosporine A (CsA), a fungal undecapepticie, 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 II
(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 (ATI) receptor
antagonist, candesartan, on CsA- induced nephrotoxicity.
Three groups of rats were employed in this study; group I
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 fiowometer. 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
candesartan. These results clearly demonstrate the pivotal
role of ATI receptor antagonist candesartan in CsA- induced
nephrotoxicity. |
