Effect of Flavonoids on Daunorubicin-induced Toxicity in H9c2 Cardiomyoblasts

Daunorubicin (DNR) is one of the most important antitumor agents belonging to the anthracycline group. However, its use is seriously limited by the development of cardiac toxicity. The present study was designed to investigate the effects of quercetin, pycnogenol and naringenin on daunorubicin-induced cytoxicity in H9c2 cells. Protection of H9c2 cardiomyocyte cells was concentration/dose dependent for quercetin > naringenin > pycnogenol = trolox. Quercetin ( 10(-4)-10(-5) mol/L) after 24 h of co-incubation with DNR significantly increased the cardiomyocyte survival (p < 0.001 and p < 0.05, respectively). A protective effect of other compounds was observed only in the highest concentration/dose used (p < 0.01). After 48 h of incubation quercetin and naringenin significantly decreased daunorubicin-induced cell death at concentrations of 10(-4)-10(-5) mol/L (p < 0.001 and p < 0.01, respectively). The protective effect of pycnogenol and trolox was weaker but significant in the two highest concentrations/doses (p < 0.001 and p < 0.05, respectively). This study also investigated DNR-induced apoptosis and it was shown that both quercetin and naringenin inhibit apoptosis of H9c2 cardiomyocytes cells in vitro. The findings provide evidence that quercetin and naringenin may act as survival factors. The protective effect of flavonoids was compared with that of trolox, a known cardioprotective antioxidant. These results are consistent with the notion that the use of flavonoids may be beneficial in modulating or preventing the cardiotoxicity associated with DNR therapy. Copyright (c) 2008 John Wiley & Sons, Ltd.