Protective effect of Epo on oxidative renal injury in rats with cyclosporine nephrotoxicity
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ORIGINAL ARTICLE
Protective effect of Epo on oxidative renal injury in rats with cyclosporine nephrotoxicity Belde Kasap & Alper Soylu & Filiz Kuralay & Sülen Sarioglu & Müge Kiray & Kazım Tuğyan & Mehmet Türkmen & Salih Kavukcu
Received: 26 December 2007 / Revised: 8 May 2008 / Accepted: 9 May 2008 / Published online: 11 July 2008 # IPNA 2008
Abstract The aim of our study was to determine the effect of recombinant human erythropoietin (rhEPO) on cyclosporine (CsA) nephrotoxicity. Twenty-six female Wistar rats were injected with 15 mg/kg subcutaneous CsA and intraperitoneal saline/rhEPO for 28 days. Four groups were formed: Group 1 (n = 5), a control group; Group 2 (n = 7), CsA + saline; Group 3 (n = 7), CsA + low dose (20 U/kg per day) rhEPO; Group 4 (n = 7), CsA + high dose (100 U/kg per day) rhEPO. Body weights, creatinine clearance, urinary protein/ creatinine, hematocrit, serum creatinine levels, histopathological parameters, apoptosis and lipid peroxidation tests were compared between the three groups. Body weights and renal functions were similar in Groups 2, 3 and 4 rats but significantly lower than the values found for the control
group at the end of the study. The hematocrit was significantly different between the four groups, showing a positive association with the strength of the injected rhEPO doses. Tubular and arteriolar damage was significantly lower in Groups 3 and 4 rats than in Group 2 rats, while chronic changes were similar between the three groups. TUNELpositive cells and thiobabarbituric acid reacting substances (TBARS) levels were significantly higher in Group 2 rats, whereas superoxide dismutase levels were significantly lower in Group 2 rats than in those of the other three groups. Low or high dose rhEPO had no significant protective effects on body weight, renal functions, chronic fibrotic changes, but both doses reduced tubular and arteriolar changes, apoptotis and oxidative stress.
B. Kasap : A. Soylu : M. Türkmen : S. Kavukcu Department of Pediatrics, Faculty of Medicine, Dokuz Eylül University, İnciraltı, İzmir, Turkey
Keywords Cyclosporine . Erythropoietin . Nephrotoxicity . Oxidative injury . Rat
F. Kuralay Department of Biochemistry, Faculty of Medicine, Dokuz Eylül University, İnciraltı, İzmir, Turkey S. Sarioglu Department of Pathology, Faculty of Medicine, Dokuz Eylül University, İnciraltı, İzmir, Turkey M. Kiray : K. Tuğyan Department of Histology, Faculty of Medicine, Dokuz Eylül University, İnciraltı, İzmir, Turkey S. Kavukcu (*) Mithatpasa Cad. No: 665/4, 35280 Kucukyalı, İzmir, Turkey e-mail: [email protected]
Introduction Cyclosporine (CsA) is one of the most widely used immunosuppressive drugs in organ transplantation and autoimmune disorders. However, its clinical use is limited by its nephrotoxicity, which includes early reversible changes in hemodynamics followed by irreversible injuries characterized by tubular vacuolization, tubular necrosis, tubulointerstitial fibrosis and afferent arteriolopathy [1, 2]. Renal cell apoptosis and processes associated with re
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