Cytoprotective effect of anthocyanins against doxorubicin-induced toxicity in H9c2 cardiomyocytes in relation to their antioxidant activities

The effect of six anthocyanidins and seven anthocyanins against doxorubicin (Dox)-induced cardiotoxicity in relation to their antioxidant properties was investigated in H9c2 cardiomyocytes. The exposure to Dox, a highly effective cytotoxic agent against cancer cells, induced significant cell death, intracellular reactive oxygen species (ROS), and lipid peroxidation in non-tumorigenic cardiac cell culture. All anthocyanidins (50 and/or 100 μM) significantly increased cell survival up to 40% compared to the Dox-treated controls. Especially, cyanidin and delphinidin, which have an ortho-dihydroxyl moiety (3′,4′-OH) on the flavylium skeleton, demonstrated the most potent protection against cytotoxicity (EC50 of 113 and 179 μM, respectively) as well as lipid peroxidation induced by Dox treatment. In contrast, seven anthocyanins having a glycosidic moiety showed little effect in cytoprotection and lipid peroxidation, although they markedly blocked intracellular ROS generation. All anthocyanidins and anthocyanins had higher TEAC values than ascorbic acid, and efficaciously scavenged superoxide anion (O2-), hydrogen peroxide (H2O2), peroxynitrite (ONOO−) and nitric oxide (NO), but not hydroxyl radical (OH). Their O2- scavenging activity was well correlated with the observed cytoprotection (r = 0.67, p < 0.05). These results suggest that anthocyanidins can ameliorate Dox-induced cardiotoxicity by, at least in part, scavenging of O2- generated by Dox.