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 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.
Keywords Cyclosporine - Erythropoietin - Nephrotoxicity - Oxidative injury - Rat