The effect of low-dose continuous erythropoietin receptor activator in an experimental model of acute Cyclosporine A induced renal injury

Autor: Stephan Arni, Walter Weder, Ilhan Inci, Christian M Meerwein, Wolfgang Jungraithmayr, Stephan Korom
Přispěvatelé: University of Zurich, Jungraithmayr, W
Rok vydání: 2011
Předmět:
Male
medicine.medical_specialty
10255 Clinic for Thoracic Surgery
Cell Survival
medicine.medical_treatment
Antigens
Differentiation
Myelomonocytic
Renal function
610 Medicine & health
Kidney
Organ transplantation
Polyethylene Glycols
Nephrotoxicity
Rats
Sprague-Dawley
Transforming Growth Factor beta1
Islets of Langerhans
Antigens
CD
Internal medicine
medicine
Animals
Osteopontin
Erythropoietin
Pharmacology
Hematologic Tests
Dose-Response Relationship
Drug
biology
business.industry
Macrophages
Insulin
Body Weight
Acute Kidney Injury
medicine.disease
Interleukin-10
Rats
Continuous erythropoietin receptor activator
Disease Models
Animal
10022 Division of Surgical Research
3004 Pharmacology
Glucose
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Cyclosporine
biology.protein
Pancreatic injury
business
Zdroj: European Journal of Pharmacology. 671:113-119
ISSN: 0014-2999
DOI: 10.1016/j.ejphar.2011.09.166
Popis: 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-β1) and RT-PCR (TGF-β1, 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-β1 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.
Databáze: OpenAIRE
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