The Effects of Valsartan on Renal Klotho Expression and Oxidative stress in Alleviation of Cyclosporine Nephrotoxicity.

Background: Nephrotoxicity side effect of the immunosuppressive drug, Cyclosporine-A (CsA), can be a major issue in transplantation medicine. CsA-induced nephrotoxicity is multifactorial but oxidative stress has a critical role in this process. It has been demonstrated that Valsartan (Val) as an angiotensin receptor blocker has renoprotective effects, but the molecular mechanisms responsible for the renal protection, independent from its blood pressure lowering effect, have not yet been fully understood. The present study is aim at evaluating the Val effect in alleviation of CsA nephrotoxicity by probable increase in renal Klotho expression and/or reducing oxidative stress. Methods: 32 Sprague-Dawley rats were divided into 4 groups based on the administration of CsA and/or Val: Group A (Control, 1 mL/kg/day of olive oil as vehicle), Group B (CsA, 30 mg/kg/day), Group C (CsA+Val, 30+30 mg/kg/day) and Group D (Val, 30 mg/kg/day). Real-time PCR and western blotting were used to evaluate Renal Klotho expression. Serum Klotho level was measured by enzyme-linked immunosorbent assay (ELISA). 8-Hydroxy-deoxy guanosine (8-OHdG) and Malondialdehyde (MDA) levels as markers of oxidative stress were measured by ELISA and spectrophotometrically respectively. Results: CsA treatment reduced renal expression and serum levels of Klotho, improved MDA and 8-OHdG levels, and also deteriorated renal function. Val prevented CsA-induced oxidative stress as well as Klotho downregulation and could alleviate CsA-induced renal histological changes and function. Conclusion: Administration of Val might lead to amelioration of CsA nephrotoxicity by probably diminishing CsA-induced renal Klotho downregulation and oxidative stress. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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