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 ( ). However, these biomarkers significantly decreased by erythropoietin ( ). 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 ( ). Conclusion. It seems that erythropoietin could protect the kidney against cisplatin-induced nephrotoxicity. This protective effect was not observed when estrogen was present. 1. Introduction Cisplatin (cis-diamminedichloroplatinum II, CP) as a potent antitumor drug is commonly used for a wide variety of tumors, including head and neck, lung, testis, ovary, and breast tumors [1]. However, it has many side effects like ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. The main dose-limiting side effect of CP is nephrotoxicity [2]. CP injection leads to accumulation of platinum within kidney tissue and influences renal tubular function [3]. The renal dysfunction following exposure to CP is involved in tubular epithelial cell toxicity, apoptosis, vasoconstriction in the renal microvasculature, proinflammatory effects, and activation of mitogen-activated protein kinases [4, 5]. These events lead to wasting of sodium, potassium, magnesium, elevation in serum levels of creatinine (Cr) and blood urea nitrogen (BUN), reduction in serum albumin, and decrease in the glomerular filtration rate [2, 3, 5]. Many agents such as vitamins C and E, losartan, and l-arginine have been proposed to protect the kidney against nephrotoxicity of platinum drugs [6–8]. EPO is one of these agents used for treatment of anemia and acute renal failure induced by CP [9, 10]. EPO
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