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Hydrocortisone attenuates cyclosporin A-induced nephrotoxicity in rats
Authors:Ciarcia Roberto  Damiano Sara  Fiorito Filomena  Granato Giovanna  Pagnini Francesco  Mastellone Vincenzo  Iovane Valentina  Alfano Luigi  Valenti Fabio  Florio Salvatore  Giordano Antonio
Affiliation:Department of Structures, Functions and Biological Technologies, School of Veterinary Medicine, University of Naples, Federico II, Naples, Italy. roberto.ciarcia@unina.it
Abstract:Cyclosporin A (CsA) is the prototype of immunosuppressant drugs that have revolutionized the management of all transplantation and autoimmune diseases. Side effects of CsA mainly affecting the kidney but also observed in liver and heart, limit the therapeutic use of this drug after organ transplantation. The renal toxicity of CsA is attributed to reduced renal blood flow which leads to hypoxia-reoxygenation injury accompanied by excessive generation of oxygen-derived free radicals. In several therapeutic protocols, CsA is used in association with corticosteroids to obtain better therapeutic results. Recently, our studies showed that hydrocortisone (HY) has a protective effect on CsA-induced cardiotoxicity. In fact our previous results demonstrated that in rat cardiomyocytes, CsA toxicity is due to a calcium overload, which in turn induce lipid peroxidation and determines oxidative stress-induced cell injury. Treatment with HY effectively inhibits CsA-induced toxicity, decreasing lipid peroxidation as well as calcium intracellular concentration. In this study we evaluated in vivo the effects of CsA, used alone or in association with HY, on some parameters of renal dysfunction (blood urea nitrogen; BUN, creatinine, and cholesterol), malondialdheyde (MDA) levels, antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and apoptosis. CsA administration for 24 days resulted in a marked renal oxidative stress, which significantly deranged the renal functions. Treatment with CsA in association with HY significantly improved the renal dysfunction and renal oxidative status. This study clearly suggests the role of oxidative stress in the pathogenesis of CsA-induced nephrotoxicity.
Keywords:CYCLOSPORIN A  SUPEROXIDE DISMUTASE  NEPHROTOXICITY  CATALASE  LIPID PEROXIDATION
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