title: Protection against cisplatin-induced nephrotoxicity by recombinant human erythropoietin.
abstract: Cisplatin (CDDP) is a potent nephrotoxin, and nephrotoxicity is its most important dose-limiting toxicity. In this study, we aimed to investigate the role of recombinant human erythropoietin (rhEPO) in the protection of cisplatin-induced nephrotoxicity and compare its efficacy with the cell-protective agent amifostine. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to four groups, each including six rats. Group A received only CDDP, group B received CDDP plus rhEPO, group C received CDDP plus amifostine, and group D received only rhEPO. At the end of 7 wk, hemoglobin (Hgb), hematocrite (Htc), blood urea nitrogen (BUN), and creatinine (Cr) levels were determined and kidneys of the rats were removed. The weights of the kidneys were measured and sent for histopathological examination. Proximal tubules from four areas of the kidney (outer cortex, inner cortex, the medullary ray, and outer stripe of outer medulla [OSOM]) were evaluated. There were statistically significant differences among the groups in terms of tubular scores, including overall renal tubular score, cortex, inner cortex, OSOM, and medullary ray tubular scores, and Htc levels. Group A rats had the worse tubular scores in all categories when compared to group D rats. When the results of groups B and C were compared, there were no differences in terms of BUN, Cr levels, and tubular scores, but the Htc level was significantly higher in group B. Group B rats had better overall and OSOM tubular scores when compared to group A. Group C also had better overall and OSOM tubular scores compared to group A. The present study showed for the first time that rhEPO plays an important role in the prevention of cisplatin-induced nephrotoxicity and it is as effective as amifostine.
authors.affiliation: Institute of Oncology, School of Medicine, Department of Histology, Hacettepe University, Sihhiye, 06100 Ankara, Turkey. syalcin@hacettepe.edu.tr
authors.forename: Suayib
authors.initials: S
authors.lastname: Yalcin
authors.forename: Sevda
authors.initials: S
authors.lastname: Müftüoğlu
authors.forename: Eren
authors.initials: E
authors.lastname: Cetin
authors.forename: Banu
authors.initials: B
authors.lastname: Sarer
authors.forename: Berna Akkuş
authors.initials: BA
authors.lastname: Yildirim
authors.forename: Dilara
authors.initials: D
authors.lastname: Zeybek
authors.forename: Bülent
authors.initials: B
authors.lastname: Orhan
mesh_terms: D004999:Amifostine / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D007668:Kidney / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
chemical_list: D000970:Antineoplastic Agents; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D003404:Creatinine; D004999:Amifostine; D002945:Cisplatin