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重组人促红细胞生成素对顺铂诱导的肾毒性的保护作用。

Protection against cisplatin-induced nephrotoxicity by recombinant human erythropoietin.

作者信息

Yalcin Suayib, Müftüoğlu Sevda, Cetin Eren, Sarer Banu, Yildirim Berna Akkuş, Zeybek Dilara, Orhan Bülent

机构信息

Institute of Oncology, School of Medicine, Department of Histology, Hacettepe University, Sihhiye, 06100 Ankara, Turkey.

出版信息

Med Oncol. 2003;20(2):169-74. doi: 10.1385/MO:20:2:169.

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.

摘要

顺铂(CDDP)是一种强效肾毒素,肾毒性是其最重要的剂量限制性毒性。在本研究中,我们旨在探讨重组人促红细胞生成素(rhEPO)在保护顺铂诱导的肾毒性中的作用,并将其疗效与细胞保护剂氨磷汀进行比较。所有实验均在雌性Wistar白化大鼠身上进行。动物被随机分为四组,每组包括六只大鼠。A组仅接受顺铂,B组接受顺铂加rhEPO,C组接受顺铂加氨磷汀,D组仅接受rhEPO。在7周结束时,测定血红蛋白(Hgb)、血细胞比容(Htc)、血尿素氮(BUN)和肌酐(Cr)水平,并摘除大鼠的肾脏。测量肾脏重量并送去进行组织病理学检查。评估肾脏四个区域(外皮质、内皮质、髓放线和外髓质外层[OSOM])的近端小管。各组在肾小管评分方面存在统计学显著差异(包括总体肾小管评分、皮质、内皮质、OSOM和髓放线肾小管评分)以及Htc水平。与D组大鼠相比,A组大鼠在所有类别中的肾小管评分都更差。比较B组和C组的结果时,在BUN、Cr水平和肾小管评分方面没有差异,但B组的Htc水平显著更高。与A组相比,B组大鼠的总体和OSOM肾小管评分更好。与A组相比,C组的总体和OSOM肾小管评分也更好。本研究首次表明,rhEPO在预防顺铂诱导的肾毒性中起重要作用,且其效果与氨磷汀相当。

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