Hydrocortisone attenuates cyclosporin A-induced nephrotoxicity in rats

Roberto Ciarcia, Sara Damiano, Filomena Fiorito, Giovanna Granato, Francesco Pagnini, Vincenzo Mastellone, Valentina Iovane, Luigi Alfano, Fabio Valenti, Salvatore Florio, Antonio Giordano

Research output: Contribution to journalArticlepeer-review

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 CsAinduced 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.

Original languageEnglish
Pages (from-to)997-1004
Number of pages8
JournalJournal of Cellular Biochemistry
Volume113
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Catalase
  • CYClosporin A
  • Lipid Peroxidation
  • Nephrotoxicity
  • Superoxide Dismutase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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