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5-氟尿嘧啶对阿霉素心脏毒性的抑制作用:一种潜在的游离氧自由基清除剂。

Inhibition of adriamycin cardiotoxicity by 5-fluorouracil: a potential free oxygen radical scavenger.

作者信息

Stathopoulos G P, Malamos N A, Dontas I, Deliconstantinos G, Perrea-Kotsareli D, Karayannacos P E

机构信息

Hippokration-Oncology Department, School of Medicine, University of Athens, Greece.

出版信息

Anticancer Res. 1998 Nov-Dec;18(6A):4387-92.

PMID:9891497
Abstract

Adriamycin (ADR), a broad spectrum anticancer agent, has a limit to total dose used, due to cumulative cardiotoxicity. This side effect has been tested in the present study in combined administration with 5-fluorouracil a cytotoxic drug that often is applied together with ADR in cancer treatment. The study was performed on Wistar rats, and the experiment consisted of weekly administration for 12 weeks of adriamycin alone, of 5-fluorouracil alone, a combination of both, and a control group (normal saline) in separate groups comprising 42 animals each. The histology of the cardiac muscle, large vessels and liver, biochemistry of serum cholesterol, triglycerides and HDL-C and oxygen free radical production were examined. It was found that addition of 5-FU to the ADR administration reduced significantly the cardiac lesions, delayed and reduced the increase of serum lipids, produced by ADR alone and oxygen free radical production was also reduced, indicating that 5-fluorouracil is acting as a scavenger of free radicals.

摘要

阿霉素(ADR)是一种广谱抗癌药物,由于累积性心脏毒性,其使用的总剂量有限。在本研究中,对这种副作用进行了测试,将其与5-氟尿嘧啶联合给药,5-氟尿嘧啶是一种细胞毒性药物,在癌症治疗中常与阿霉素一起使用。该研究以Wistar大鼠为对象,实验包括单独每周给药阿霉素12周、单独给药5-氟尿嘧啶、两者联合给药以及一个对照组(生理盐水),每组有42只动物。对心肌、大血管和肝脏进行了组织学检查,检测了血清胆固醇、甘油三酯和高密度脂蛋白胆固醇的生化指标以及氧自由基的产生。结果发现,在阿霉素给药中加入5-氟尿嘧啶可显著减轻心脏病变,延缓并减轻单独使用阿霉素引起的血脂升高,同时氧自由基的产生也减少,这表明5-氟尿嘧啶起到了自由基清除剂的作用。

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