Doxorubicin is a chemotherapy drug used to treat many different forms of cancer. It works by interfering with the function of DNA in rapidly dividing cells. Cancer cells divide particularly rapidly, and doxorubicin can cause them to die. However, certain types of normal body cells also divide rapidly; doxorubicin damages them as well. This leads to a variety of possible side effects, including hair loss, digestive problems, reduced immunity, excessive bruising or bleeding, anemia, mouth sores and male infertility. Doxorubicin can also damage the heart and kidneys, apparently by interfering with the action of the mitochondria in heart cells. (Mitochondria are the energy-producing subunits of cells.)
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It is hypothesized that many of the side effects of doxorubicin occur through the production of free radicals, dangerous substances that can harm many cells. Antioxidants scavenge or quench free radicals. On this basis, a number of antioxidants have been proposed as a treatment for reducing doxorubicin toxicity. Unfortunately, while some evidence of benefit has been seen in animal studies, at present there is inadequate supporting evidence from human trials.
The supplement melatonin has also shown some promise in animal studies for reducing the cardiac toxicity of doxorubicin; however, the only human trials supporting this use fall considerably beneath modern scientific standards.1-8
According to animal studies, lycopene might help protect the heart and also shield developing sperm cells from injury (thereby reducing male infertility);13-15 the herbal extract curcumin might help prevent damage to the heart and kidneys;19,20n-acetyl cysteine might help protect the heart and also reduce hair loss;21-22lipoic acid16-17 and coenzyme Q1018 might protect the heart. However, for all of these antioxidants, support from human trials is lacking. One animal study hints at potential heart- and liver-protective effects with the supplement carnitine.23
1. Wahab MH, Akoul ES, Abdel-Aziz AA. Modulatory effects of melatonin and vitamin E on doxorubicin-induced cardiotoxicity in Ehrlich ascites carcinoma-bearing mice. Tumori. 2000;86:157-62.
2. Oz E, Ilhan MN. Effects of melatonin in reducing the toxic effects of doxorubicin. Mol Cell Biochem. 2006;286:11-5.
3. Oz E, Erbas D, Surucu HS et al. Prevention of doxorubicin-induced cardiotoxicity by melatonin. Mol Cell Biochem. 2005;282:31-7.
4. Kim C, Kim N, Joo H et al. Modulation by melatonin of the cardiotoxic and antitumor activities of adriamycin. J Cardiovasc Pharmacol. 2005;46:200-10.
5. Balli E, Mete UO, Tuli A et al. Effect of melatonin on the cardiotoxicity of doxorubicin. Histol Histopathol. 2004;19:1101-8.
6. Kocak G, Erbil KM, Ozdemir I et al. The protective effect of melatonin on adriamycin-induced acute cardiac injury. Can J Cardiol. 2003;19:535-41.
7. Reiter RJ, Tan DX, Sainz RM et al. Melatonin: reducing the toxicity and increasing the efficacy of drugs. J Pharm Pharmacol. 2002;54:1299-321.
8. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer. 1999;35:1688-92.
9. Puri A, Maulik SK, Ray R et al. Electrocardiographic and biochemical evidence for the cardioprotective effect of vitamin E in doxorubicin-induced acute cardiotoxicity in rats. Eur J Pediatr Surg. 2006;15:387-91.
10. Berthiaume JM, Oliveira PJ, Fariss MW et al. Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction. Cardiovasc Toxicol. 2005;5:257-67.
11. Wahab MH, Akoul ES, Abdel-Aziz AA. Modulatory effects of melatonin and vitamin E on doxorubicin-induced cardiotoxicity in Ehrlich ascites carcinoma-bearing mice. Tumori. 2000;86:157-62.
12. Legha SS, Wang YM, Mackay B et al. Clinical and pharmacologic investigation of the effects of alpha-tocopherol on adriamycin cardiotoxicity. Ann N Y Acad Sci. 1983;393:411-8.
13. Atessahin A, Turk G, Karahan I et al. Lycopene prevents adriamycin-induced testicular toxicity in rats. Fertil Steril. 2006;85 Suppl 1:1216-22.
14. Yilmaz S, Atessahin A, Sahna E et al. Protective effect of lycopene on adriamycin-induced cardiotoxicity and nephrotoxicity. Toxicology. 2005;218:164-71.
15. Karimi G, Ramezani M, Abdi A. Protective effects of lycopene and tomato extract against doxorubicin-induced cardiotoxicity. Phytother Res. 2005;19:912-4.
16. Balachandar AV, Malarkodi KP, Varalakshmi P. Protective role of DL alpha-lipoic acid against adriamycin-induced cardiac lipid peroxidation. Hum Exp Toxicol. 2003;22:249-54.
17. Al-Majed AA, Gdo AM, Al-Shabanah OA, et al. Alpha-lipoic acid ameliorates myocardial toxicity induced by doxorubicin. Pharmacol Res. 2002;46:499-503.
18. Conklin KA. Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity. Integr Cancer Ther. 2005;4:110-30.
19. Venkatesan N. Curcumin attenuation of acute adriamycin myocardial toxicity in rats. Br J Pharmacol. 1998;124:425-7.
20. Venkatesan N, Punithavathi D, Arumugam V. Curcumin prevents adriamycin nephrotoxicity in rats. Br J Pharmacol. 2000;129:231-4.
21. D'Agostini F, Bagnasco M, Giunciuglio D et al. Inhibition by oral N-acetylcysteine of doxorubicin-induced clastogenicity and alopecia, and prevention of primary tumors and lung micrometastases in mice. Int J Oncol. 1998;13:217-24.
22. Dorr RT. Cytoprotective agents for anthracyclines. Semin Oncol. 1996;23:23-34.
23. Strauss M, Porras N. Differential expression of HSP70 and ultrastructure of heart and liver tissues of rats treated with adriamycin: protective role of L-carnitine. Invest Clin. 2007;48:33-43.
Last reviewed December 2015 by EBSCO CAM Review Board
Last Updated: 12/15/2015
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