Coudray C, Hida H, Boucher F, De Leiris J, Favier A
Laboratoire de Biochimie C, Centre Hospitalier Régional de Grenoble, France.
Nutrition. 1995 Sep-Oct;11(5 Suppl):512-6.
Adriamycin (doxorubicin) is an antineoplastic drug used to treat various cancers; however, its chronic use is accompanied by cardiotoxicity. Previous results suggested that free radical formation may contribute to Adriamycin toxicity. Adriamycin-induced cardiotoxicity was examined in rats maintained on either standard or selenium-supplemented diets. Adriamycin was administered intraperitoneally; the cumulative dose was 15 mg/kg body weight. Selenium status, glutathione peroxidase activities, vitamin E, and MDA contents were determined on red blood cell (RBC) and cardiac homogenates. RBC selenium levels and selenium glutathione peroxidase activity were significantly increased in selenium-supplemented animals compared with control or placebo groups. However, Adriamycin-treated rats showed a significant decrease in RBC selenium and selenium glutathione peroxidase compared with the placebo group. Moreover, treatment with Adriamycin increased RBC MDA content, which was attenuated by the selenium supplementation. In parallel, RBC vitamin E decreased markedly in the Adriamycin-treated group and was totally restored by selenium supplementation. Cardiac biochemical analyses confirmed the blood results. Thus, a free radical mechanism does contribute to Adriamycin cardiotoxicity, and shows the importance of balancing selenium levels in Adriamycin-treated subjects to limit Adriamycin's action. A decrease in Adriamycin cardiotoxicity with no concomitant decrease in its antineoplastic activity would considerably improve the therapeutic benefit of the drug.
阿霉素（多柔比星）是一种用于治疗多种癌症的抗肿瘤药物；然而，长期使用会伴有心脏毒性。先前的研究结果表明，自由基的形成可能与阿霉素毒性有关。在喂食标准饮食或补充硒饮食的大鼠中检测阿霉素诱导的心脏毒性。阿霉素通过腹腔注射给药；累积剂量为15毫克/千克体重。测定红细胞（RBC）和心脏匀浆中的硒状态、谷胱甘肽过氧化物酶活性、维生素E和丙二醛（MDA）含量。与对照组或安慰剂组相比，补充硒的动物红细胞硒水平和硒谷胱甘肽过氧化物酶活性显著增加。然而，与安慰剂组相比，阿霉素治疗的大鼠红细胞硒和硒谷胱甘肽过氧化物酶显著降低。此外，阿霉素治疗增加了红细胞MDA含量，而补充硒可使其减弱。同时，阿霉素治疗组红细胞维生素E显著降低，补充硒后完全恢复。心脏生化分析证实了血液检测结果。因此，自由基机制确实与阿霉素心脏毒性有关，并表明在接受阿霉素治疗的患者中平衡硒水平以限制阿霉素作用的重要性。在不伴随抗肿瘤活性降低的情况下降低阿霉素心脏毒性将大大提高该药物的治疗效果。
