Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity

BACKGROUND Xinfuli Granule (XG), a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with doxorubicin-induced cardiotoxicity. METHODS Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin (DOX, 2.5 mg/kg per week) for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline (control group) or different dosage of XG (0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively) for six weeks. Transthoracic echocardiography was performed to evaluate the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. RESULTS Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. CONCLUSIONS Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.