Doxorubicin (DOXO) is one of the most widely used and successful antineoplastic drugs in treating hematologic cancers and malignant neoplasms in both adults and children, however, its clinical use is seriously limited due to the development of acute and chronic cardiotoxicity leading to cardiomyopathy and congestive heart failure throughout life. Although the molecular pathogenesis of anthracycline cardiotoxicity remains to be clarified several investigations have proved that intramyocardial production of reactive oxygen species has been the primary cause of DOXO-induced cardiotoxicity. This oxidative stress-based hypothesis sheds light on the development of protective strategies using natural antioxidants without altering therapeutic effectiveness of DOXO. Bioactive plant constituents of dietary supplements with potential beneficial implications in human health can play an important role against DOXO-induced cardiac side effects. In this regard, dietary polyphenols, in particular flavonoids, are abundant micronutrients in our diet and emerging evidence suggest a potential protective role in the prevention of degenerative diseases such as cardiovascular diseases due to their pleiotropic anti-oxidative and anti-inflammatory effects. In this review we summarizes what is known about the basic molecular mechanisms by which DOXO induced oxidative stress and findings of studies undertaken to identify the cardioprotective properties of polyphenols during DOXO chemotherapy.
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