Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 671, Issue 1-3, Pages 113-119Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2011.09.166
Keywords
CERA; Cyclosporine A; Rat kidney; Pancreatic injury
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The use of Cyclosporine A (CsA) as rejection prophylaxis following organ transplantation is limited by its nephrotoxicity. CsA induces renal damage that is associated with tubulo-interstitial injury and parenchymal sequestration of macrophages, perpetuating pro-inflammatory processes. Furthermore, CsA exerts a diabetogenic effect by damaging pancreatic islet cell integrity. Continuous Erythropoietin Receptor Activator (CERA) was shown to mediate tissue-protective and anti-inflammatory effects in various settings of organ injury. Here, we investigated the effect of low dose CERA in a model of CsA-induced renal and pancreatic injury. Rats were exposed to medium-dose CsA for 28 days. Low-dose CERA was given to the treatment group (CERA) (n = 6) once per week vs. a CsA-treated control group (CONTROL) (n = 6). The effect of CERA on renal and pancreatic injuries was analyzed by organ function, histology, immunohistochemistry (CD68(+)-macrophages, insulin), ELISA (TGF-beta 1) and RT-PCR (TGF-beta 1, Osteopontin, IL-10). CsA induced functional kidney damage. Low dose CERA did not lead to improved kidney function in the treatment group. However, low dose CERA showed a trend toward upregulation of osteopontin accompanied by increased renal macrophage-infiltration and enhanced parenchymal TGF-beta 1 and IL-10 when compared to controls. Moreover, CERA treated animals showed amelioration of pancreatic islet cell injury. In this model of acute CsA-mediated renal injury, low dose CERA administration was associated with anti-inflammatory effects and preservation of pancreatic islet cell viability. (C) 2011 Elsevier B.V. All rights reserved.
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