Estrogen Abolishes Protective Effect of Erythropoietin against Cisplatin-Induced Nephrotoxicity in Ovariectomized Rats

Abstract

Introduction. Nephrotoxicity is one the side effect of cisplatin therapy and erythropoietin has been candidate as a nephroprotectant agent. However, its nephroprotective effect when it is accompained with estrogen has not been studied in female. Methods. 27 ovariectomized female Wistar rats divided into five groups. Groups 1 & 2 received estradiol valerate (0.5 mg/kg/week) for four weeks, and single dose of cisplatin (7 mg/kg, ip) was administrated at the end of week 3. Then the group 1 was treated with erythropoietin (100 U/kg/day), and the group 2 received vehicle during week 4. Groups 3 and 4 were treated similar to group 1 and 2, except for placebo instead estradiol valerate. Group5 (negative control) received placebo during the study. Animals were killed at the end of week 4. Results. In non-erythropoietin treated rats, cisplatin significantly increased the serum levels of blood urea nitrogen and creatinine (P<0.05). However, these biomarkers significantly decreased by erythropoietin (P<0.05). The weight loss, kidney weight, and kidney tissue damage score in rats treated with cisplatin but without estradiol were significantly less than the values in similar group when estradiol was present (P<0.05). Conclusion. It seems that erythropoietin could protect the kidney against cisplatin-induced nephrotoxicity. This protective effect was not observed when estrogen was present.