Natural Products Counteracting Cardiotoxicity during Cancer Chemotherapy: The Special Case of Doxorubicin, a Comprehensive Review

Abstract

Cardiotoxicity is a frequent undesirable phenomenon observed during oncological treatment that limits the therapeutic dose of antitumor drugs and thus may decrease the effectiveness of cancer eradication. Almost all antitumor drugs exhibit toxic properties towards cardiac muscle. One of the underlying causes of cardiotoxicity is the stimulation of oxidative stress by chemotherapy. This suggests that an appropriately designed diet or dietary supplements based on edible plants rich in antioxidants could decrease the toxicity of antitumor drugs and diminish the risk of cardiac failure. This comprehensive review compares the cardioprotective efficacy of edible plant extracts and foodborne phytochemicals whose beneficial activity was demonstrated in various models in vivo and in vitro. The studies selected for this review concentrated on a therapy frequently applied in cancer, anthracycline antibiotic-doxorubicin-as the oxidative stress- and cardiotoxicity-inducing agent.

Keywords: anthracyclines; antioxidants; cardioprotectants; cardiotoxicity; phytochemicals.

Figure 1

The oxidative-stress-associated cardiotoxic effects of DOX (left-hand side bars) are compared with cardioprotective activity of fruit extracts (right-hand side bars). Fruit extracts decreased MDA formation stimulated by DOX (control MDA values ranged from 7.92 to 182.65 nmol/g protein). The tested cardioprotectants restored the reduced by DOX level of GSH (control GSH values range was from 27.51 to 35.87 mg/g protein) as well as normalized activity of antioxidant enzymes SOD and CAT (100% CAT and SOD were in the range from 30.95 to 50.29 U/g protein and from 13.78 to 155.5 kU/mg protein, respectively).

Figure 2

The oxidative-stress-associated cardiotoxic effects of DOX (left-hand side bars) are compared with cardioprotective activity of bioactive phytochemicals (right-hand side bars). Phytochemicals decreased MDA formation stimulated by DOX (control MDA values ranged from 57.7 to 1179 nmol/g protein). The tested cardioprotectants restored the level of GSH reduced by DOX (control GSH values range was from 0.01 to 99.8 μmol/g protein), as well as normalized activity of antioxidant enzymes SOD and CAT (100% CAT and SOD were in the range of 5.82 to 12.35 U/mg protein and from 1.10 to 8.69 U/mg protein, respectively).

Figure 3

Experimental schemes for assessment of cardioprotective properties of beetroot tested in leukemia-bearing mice treated with DOX.