Conklin Kenneth A
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1778, USA.
Integr Cancer Ther. 2005 Jun;4(2):110-30. doi: 10.1177/1534735405276191.
Preclinical and clinical studies suggest that anthracycline-induced cardiotoxicity can be prevented by administering coenzyme Q10 during cancer chemotherapy that includes drugs such as doxorubicin and daunorubicin. Studies further suggest that coenzyme Q10 does not interfere with the antineoplastic action of anthracyclines and might even enhance their anticancer effects. Preventing cardiotoxicity might allow for escalation of the anthracycline dose, which would further enhance the anticancer effects. Based on clinical investigation, although limited, a cumulative dose of doxorubicin of up to 900 mg/m2, and possibly higher, can be administered safely during chemotherapy as long as coenzyme Q10 is administered concurrently. The etiology of the dose-limiting cardiomyopathy that is induced by anthracyclines can be explained by irreversible damage to heart cell mitochondria, which differ from mitochondria of other cells in that they possess a unique enzyme on the inner mitochondrial membrane. This enzyme reduces anthracyclines to their semiquinones, resulting in severe oxidative stress, disruption of mitochondrial energetics, and irreversible damage to mitochondrial DNA. Damage to mitochondrial DNA blocks the regenerative capability of the organelle and ultimately leads to apoptosis or necrosis of myocytes. Coenzyme Q10, an essential component of the electron transport system and a potent intracellular antioxidant, appears to prevent damage to the mitochondria of the heart, thus preventing the development of anthracycline-induced cardiomyopathy.
临床前和临床研究表明，在包括阿霉素和柔红霉素等药物的癌症化疗期间给予辅酶Q10，可以预防蒽环类药物引起的心脏毒性。研究进一步表明，辅酶Q10不会干扰蒽环类药物的抗肿瘤作用，甚至可能增强其抗癌效果。预防心脏毒性可能会使蒽环类药物剂量增加，从而进一步增强抗癌效果。基于临床研究，尽管有限，但只要同时给予辅酶Q10，化疗期间阿霉素的累积剂量高达900mg/m2甚至更高时也可安全给药。蒽环类药物引起的剂量限制性心肌病的病因可以解释为心脏细胞线粒体的不可逆损伤，心脏细胞线粒体与其他细胞的线粒体不同，其线粒体内膜上有一种独特的酶。这种酶将蒽环类药物还原为半醌，导致严重的氧化应激、线粒体能量代谢紊乱以及线粒体DNA的不可逆损伤。线粒体DNA的损伤会阻碍细胞器的再生能力，最终导致心肌细胞凋亡或坏死。辅酶Q10是电子传递系统的重要组成部分，也是一种强大的细胞内抗氧化剂，似乎可以预防心脏线粒体的损伤，从而预防蒽环类药物引起的心肌病的发生。
