Coudray C, Mouhieddine S, Richard M J, Arnaud J, De Leiris J, Favier A
Laboratoire de Biochimie C, Centre Hospitalier Régional de Grenoble, France.
Basic Res Cardiol. 1992 Mar-Apr;87(2):173-83. doi: 10.1007/BF00801964.
Adriamycin (doxorubicin) is an antineoplastic drug used to treat various cancers; however, its chronic use is unfortunately accompanied by cardiotoxicity. This toxicity can be reduced by antioxidant agents such as selenium, and it is particularly interesting that cancer patients are usually deficient in this trace element, which suggests that its supplementation could contribute to beneficial treatment. We have examined the effect of adriamycin on chronic cardiotoxicity in 6-week selenium deficiency in rats. Selenium-deficient rats showed a considerable reduction of selenium levels and of selenium-containing glutathione peroxidase. Cardiac lipid peroxides increased slightly in the deficient rats, whereas plasma and heart lipid peroxides increased markedly in adriamycin-treated rats. This increase was greatly accentuated in selenium deficiency. These results suggest that free radical mechanism may be contributing to adriamycin toxicity, and above all show the importance of balancing the selenium levels in adriamycin-treated subjects to limit its harmful myocardial action. A decrease in adriamycin cardiotoxicity with no concomitant decrease in its antineoplastic activity would be of considerable value by improving 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，不幸的是，长期使用会伴随心脏毒性。抗氧化剂如硒可以降低这种毒性，特别有意思的是癌症患者通常缺乏这种微量元素，这表明补充硒可能有助于治疗。我们研究了阿霉素对大鼠6周硒缺乏慢性心脏毒性的影响。缺硒大鼠的硒水平和含硒谷胱甘肽过氧化物酶显著降低。缺硒大鼠心脏脂质过氧化物略有增加，而阿霉素治疗的大鼠血浆和心脏脂质过氧化物显著增加。在硒缺乏时，这种增加更为明显。这些结果表明自由基机制可能与阿霉素毒性有关，最重要的是表明在接受阿霉素治疗的患者中平衡硒水平以限制其对心肌的有害作用的重要性。在不伴随阿霉素抗肿瘤活性降低的情况下降低其心脏毒性，通过提高药物的治疗效果将具有相当大的价值。
