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 language | English |
|---|---|
| Pages (from-to) | 997-1004 |
| Number of pages | 8 |
| Journal | Journal of Cellular Biochemistry |
| Volume | 113 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2012 |
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Keywords
- Catalase
- CYClosporin A
- Lipid Peroxidation
- Nephrotoxicity
- Superoxide Dismutase
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Hydrocortisone attenuates cyclosporin A-induced nephrotoxicity in rats. / Ciarcia, Roberto; Damiano, Sara; Fiorito, Filomena; Granato, Giovanna; Pagnini, Francesco; Mastellone, Vincenzo; Iovane, Valentina; Alfano, Luigi; Valenti, Fabio; Florio, Salvatore; Giordano, Antonio.
In: Journal of Cellular Biochemistry, Vol. 113, No. 3, 03.2012, p. 997-1004.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hydrocortisone attenuates cyclosporin A-induced nephrotoxicity in rats
AU - Ciarcia, Roberto
AU - Damiano, Sara
AU - Fiorito, Filomena
AU - Granato, Giovanna
AU - Pagnini, Francesco
AU - Mastellone, Vincenzo
AU - Iovane, Valentina
AU - Alfano, Luigi
AU - Valenti, Fabio
AU - Florio, Salvatore
AU - Giordano, Antonio
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Catalase
KW - CYClosporin A
KW - Lipid Peroxidation
KW - Nephrotoxicity
KW - Superoxide Dismutase
UR - http://www.scopus.com/inward/record.url?scp=84857545377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857545377&partnerID=8YFLogxK
U2 - 10.1002/jcb.23429
DO - 10.1002/jcb.23429
M3 - Article
C2 - 22034142
AN - SCOPUS:84857545377
VL - 113
SP - 997
EP - 1004
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
SN - 0730-2312
IS - 3
ER -