Tokarska-Schlattner Malgorzata, Wallimann Theo, Schlattner Uwe
Institute of Cell Biology, ETH Zurich, Hönggerberg HPM D24, CH-8093 Zürich, Switzerland.
C R Biol. 2006 Sep;329(9):657-68. doi: 10.1016/j.crvi.2005.08.007. Epub 2006 Jun 21.
Doxorubicin and other anthracyclines are among the most potent chemotherapeutic drugs for the treatment of acute leukaemia, lymphomas and different types of solid tumours such as breast, liver and lung cancers. Their clinical use is, however, limited by the risk of severe cardiotoxicity, which can lead to irreversible congestive heart failure. There is increasing evidence that essential components of myocardial energy metabolism are among the highly sensitive and early targets of doxorubicin-induced damage. Here we review doxorubicin-induced detrimental changes in cardiac energetics, with an emphasis on the emerging importance of defects in energy-transferring and -signalling systems, like creatine kinase and AMP-activated protein kinase.
阿霉素及其他蒽环类药物是治疗急性白血病、淋巴瘤以及不同类型实体瘤(如乳腺癌、肝癌和肺癌)最有效的化疗药物之一。然而,它们的临床应用受到严重心脏毒性风险的限制,这种毒性可导致不可逆的充血性心力衰竭。越来越多的证据表明,心肌能量代谢的关键成分是阿霉素诱导损伤的高度敏感和早期靶点。在此,我们综述阿霉素诱导的心脏能量学有害变化,重点关注能量传递和信号系统(如肌酸激酶和AMP激活的蛋白激酶)缺陷的新出现的重要性。