Abstract
Nephrotoxicity is a major problem of Cyclosporine A (CsA) treatment, despite its beneficial role in organ transplantation and in a variety of immunologic disorders. This study was undertaken to investigate the potential renoprotective role of telmisartan in amelioration of chronic CsA induced nephrotoxicity. The rats were randomized into 4 equal groups. Group 1 received normal saline (control), group 2 received Cremophor EL and ethanol (CsA vehicle), group 3 received CsA 25 mg/kg/day s.c and group 4 received telmisartan 3 mg/kg/day orally in addition to CsA. The rats were pair fed with a standard chow diet throughout the experiment period (8 weeks). CsA nephrotoxicity was assessed in terms of increased S.Cr (from 0.52± 0.16 to 1.29 ± 0.20 mg/ml), blood urea (from 24.69 ± 1.89 to 75.88± 2.33 mg/ml) and serum K (from 3.43 ± 0.18 to 5.23 ± 0.43 meq/l). CsA also caused significant increase (p<0.01) in MDA (from 0.74 ± 0.13 to 2.96 ± 0.43 nmol/mg protein) and significant decrease (p<0.01) in GSH and catalase in renal tissue. Telmisartan failed to restore the altered renal functions. On the other hand, it causes a significant improvement in the histological changes including the tubulointerstitial fibrosis and arteriolopathy (p<0.01). It also caused significant reduction (p<0.01) in CsA-induced oxidative stress. These findings suggested that telmisartan has a promising renoprotective effect against chronic CsA induced nephrotoxicity. Key words: Cyclosporine A, nephrotoxicity, oxidative stress, telmisartan.
Highlights
Cyclosporine A (CsA), an immunosuppressant drug, binds to cyclophilin to inhibit phosphatase calcineurin, and thereby prevents the dephosphorylation of nuclear factor of activated T-cells that is essential for synthesis of many lymphokine mediators, IL-2
At the end of experiment, rats treated with CsA only showed a significant decrease in B.W (p
Subchronic CsA treatment resulted in significant increase (p
Summary
Cyclosporine A (CsA), an immunosuppressant drug, binds to cyclophilin to inhibit phosphatase calcineurin, and thereby prevents the dephosphorylation of nuclear factor of activated T-cells that is essential for synthesis of many lymphokine mediators, IL-2. One of the most important adverse effects that restrict the use of CsA is renal toxicity (Sweetman, 2007). The term CsA nephrotoxicity (CsAN) comprises two particular and very distinct forms of renal injury. CsAinduced acute nephrotoxicity is a hemodynamically mediated phenomenon, characterized by the absence of permanent structural changes and by the reversibility with decrease or discontinuation of the drug. Underlying renal insufficiency, intravascular volume depletion; age older than 60 years, excessive dose, and concomitant use with other nephrotoxic drugs or drugs that inhibit CsA metabolism by inhibiting CYP3A system are considered as risk factors for CsAN (Naughton, 2008)
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