College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
Toxicol Mech Methods. 2006;16(9):501-6. doi: 10.1080/15376510600751962.
The aim of the present work was to investigate changes of serum erythropoietin (Epo) during cisplatin (DDP)-or 5-Fluorouracil (5-Fu)-induced anemia in rats. Anemia was induced with single intravenous (IV) injection of DDP of 8 mg/kg body weight or 5-Fu of 150 mg/kg body weight. Serum Epo, hemoglobin (Hb), blood urea nitrogen (BUN) concentration, and reticulocyte (Ret) counts were measured 7, 21, 35, and 49 days after administration of the anticancer drugs. The changes of renal tissue were examined by light microscope. A single injection of 5-Fu decreased Ret counts and Hb concentration and increased serum Epo levels. No evident morphological abnormalities were found by light microscopy in 5-Fu-treated rats. A single injection of DDP decreased Ret counts and Hb concentration and increased BUN. Serum Epo was decreased 7 days but was increased 21 days after DDP treatment; however, serum Epo elevation was modest. Pathological examination revealed that DDP caused significant renal damage in rats. These results suggest that in 5-Fu-induced anemia, the elevated serum Epo level was due to the feedback response to anemia. In DDP-induced anemia, the elevated serum Epo level was low in relation to the level of anemia, and DDP-induced nephrotoxicity might be the main cause of changes of serum Epo.
本研究旨在探讨顺铂（DDP）或氟尿嘧啶（5-Fu）诱导的贫血大鼠血清促红细胞生成素（Epo）的变化。通过单次静脉（IV）注射 8mg/kg 体重的 DDP 或 150mg/kg 体重的 5-Fu 诱导贫血。在给予抗癌药物后 7、21、35 和 49 天测量血清 Epo、血红蛋白（Hb）、血尿素氮（BUN）浓度和网织红细胞（Ret）计数。通过光镜检查肾组织的变化。单次注射 5-Fu 可降低 Ret 计数和 Hb 浓度，增加血清 Epo 水平。光镜下未发现 5-Fu 处理大鼠有明显的形态异常。单次注射 DDP 可降低 Ret 计数和 Hb 浓度，增加 BUN。DDP 治疗后 7 天血清 Epo 降低，但 21 天增加；然而，血清 Epo 升高幅度较小。病理检查显示 DDP 可导致大鼠肾脏明显损伤。这些结果表明，在 5-Fu 诱导的贫血中，血清 Epo 水平的升高是对贫血的反馈反应所致。在 DDP 诱导的贫血中，血清 Epo 水平的升高与贫血程度相比较低，DDP 诱导的肾毒性可能是血清 Epo 变化的主要原因。
