Coenzyme Q10 for Prevention of Anthracycline-Induced Cardiotoxicity

Abstract

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.

p38 MAPK downregulates phosphorylation of Bad in doxorubicin-induced endothelial apoptosis

“…It has been shown that doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes involves formation of hydrogen peroxide [3,4], and it has also been reported that antioxidant treatment exerts cardioprotective effects in cancer patients receiving doxorubicin chemotherapy [5]. It was recently demonstrated that the antitumoral influence of doxorubicin can be mediated in two ways: either through targeting of the tumor endothelium or by destruction of both the tumor endothelium and tumor cells [6][7][8].…”

Dietary Supplement Use in Cancer Care: Help or Harm

“…A decreased rate of chemotherapy-related nephro-and ototoxicity was only seen in the patients-supplemented with vitamins C, E, and selenium-who achieved the highest serum levels [78]. Experts have also cited preclinical and some limited human data to support the use of coenzyme Q10 to reduce the toxicity of anthrocyclin-based chemotherapy [79]. Benefit derived from antioxidant treatment for specific side effects of treatment are discussed in subsequent sections.…”

Nutrition, Nitrogen Requirements, Exercise and Chemotherapy-Induced Toxicity in Cancer Patients. A puzzle of Contrasting Truths?

“…This is possibly due to competition for the enzyme active site. Co-Q10 administration seems to prevent damage to the cardiomyocytes mitochondria, thus, preventing the development of drug-induced cardiomyopathy [127].…”

“…This may explain the high degree of oxidative stress that the drug causes in cardiac mitochondria. Therefore, the specific structure of the electron transport system of cardiac mitochondria is responsible for the high level of oxidative stress generated by Doxo and for the development of cardiomyopathy [127].…”