Abstract

BACKGROUND: Qishen Yiqi Dropping Pills (QYDP) is a Chinese traditional medicine that has been applied to treat coronary heart disease and ischemic heart failure in China. However, few studies have explored whether QYDP exerted an effect on doxorubicin (Doxo)-induced cardiotoxicity. Hence, in this study we investigated the effect of QYDP on cardiotoxicity induced by doxorubicin (Doxo) and its potential mechanism.

MATERIAL AND METHODS: Male C57BL/6 mice (20–25 g, 8–10 weeks old) were randomly assigned to 4 groups: Control group, QYDP group, Doxo group, and QYDP+Doxo group. The mice were intraperitoneal injected with Doxo weekly for 4 weeks to mimic the chronic toxicity. Four weeks after Doxo injection, echocardiography was applied to evaluate the left ventricular (LV) function, and the structure of the cardiac muscle fibers was analyzed with anti-actinin-2 antibody staining by immunofluorescence. Moreover, TUNEL staining and western blot analysis of Bax protein, Bcl-2 protein, and cleaved caspase-3 protein expression levels were conducted to explore whether QYDP exerted effect on cardiac apoptosis. In addition, Masson trichrome staining and western blot analysis of α-SMA protein expression levels were used to evaluate whether QYDP exerted an effect on cardiac fibrosis. Western blots and quantitative real-time polymerase chain reaction were applied to detect the vascular endothelial growth factor (VEGF) protein and mRNA levels in the myocardial tissue, and anti-CD31 antibody staining by immunohistochemistry was employed to explore whether QYDP exerted an effect on cardiac angiogenesis.

RESULTS: QYDP effectively attenuated cardiac dysfunction and cardiac muscle fibers disruption in Doxo treated mice. Moreover, QYDP reduced myocardial apoptosis and myocardial fibrosis in Doxo treated mice, accompanied with elevated protein levels of VEGF and enhancement of myocardial microvessel density.

CONCLUSIONS: QYDP could protect against Doxo-induced cardiotoxicity, which may be closely associated with enhanced cardiac angiogenesis. Hence, QYDP could be a promising alternative for the treatment of Doxo-induced cardiotoxicity.

Keywords: Angiogenesis Inducing Agents, Doxorubicin, Fibrosis, Cardiomyopathies, cardiotoxicity, Drugs, Chinese Herbal, Heart, Heart Diseases, Mice, Inbred C57BL, Myocardium, Myocytes, Cardiac, Vascular Endothelial Growth Factor A, bcl-2-Associated X Protein