Doxorubicin is an important and effective anticancer drug widely used for the treatment of various types of cancer but its clinical use is limited by dose-dependent cardiotoxicity. Elevated tissue levels of cellular superoxide anion/oxidative stress are a mechanism by which doxorubicin-induced cardiotoxicity. Selected medicinal plant extracts were tested for their antioxidant capacity and cardioprotective effect against doxorubicin-induced cardiotoxicity. The cardiac myoblasts H9c2 were incubated with the antioxidants ascorbic acid, trolox, N-acetylcysteine or selected medicinal plant extracts including; 1) ethanolic extracts from Curcuma longa L-EtOH Phyllanthus emblica L-EtOH, and Piper rostratum Roxb-EtOH; and 2) water extracts from Curcuma longa L-H2O and Morus alba L-H2O. The cardioprotective effects of these extracts were evaluated by crystal violet cytotoxicity assay. IC50s of doxorubicin were compared in the presence or absence of ascorbic acids, trolox, N-acetylcysteine or plant extracts. Morus alba L-H2O showed the highest antioxidant properties evaluated by ferric reducing/antioxidant power assay. Ascorbic acid and N-acetylcysteine had modest effects on the protection of doxorubicin-induced cytotoxicity while trolox showed insignificant protective effect. All plant extracts protected cardiac toxicity at different degrees except that Curcuma longa L-EtOH had no protective effect. Phyllanthus emblica-EtOH (100 microg/ml) showed the highest cardioprotective effect (approximately 12-fold doxorubicin IC50 increase). The data demonstrate that antioxidants from natural sources may be useful in the protection of cardiotoxicity in patients who receive doxorubicin.
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