Protective effect of Epo on oxidative renal injury in rats with cyclosporine nephrotoxicity.
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. TUNEL-positive cells and thiobabarbituric acid reacting substance (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.
Kasap
Belde
B
Department of Pediatrics, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.
Soylu
Alper
A
Kuralay
Filiz
F
Sarioglu
Sülen
S
Kiray
Müge
M
Tuğyan
Kazim
K
Türkmen
Mehmet
M
Kavukcu
Salih
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D016572:Cyclosporine