title: Astragalus polysaccharide improves cardiac function in doxorubicin-induced cardiomyopathy through ROS-p38 signaling.
abstract: Doxorubicin (DOX) is widely used as an antitumor agent, but it is significantly challenged by clinical workers due to the severe and acute cardiotoxitity. Astragalus polysaccharide (APS) is characterized by an anti-inflammation and anti-oxidant features. In the current study, we explored the effects and specific mechanisms of APS on DOX-induced-cardiomyopathy in mouse primary myocardial cells. To explore the effect of DOX on ROS production, DHE staining and flow cytometry analysis were used in primary cardiomyocytes treated with 1 μM DOX for 24 h. MTT assay was applied to determine the effect of DOX on cell viability. The effects of DOX on rat cardiomyocytes apoptosis by Hoechst staining and annexin V-PI staining, while caspase3 activity was determined using an assay kit. Two-dimensional echocardiography of rats was performed to determine left ventricular fraction and relative wall thickness. Activation of p38 and Akt was analyzed using western blot. ROS production was significantly enhanced by DOX stimulation in primary cardiomyocytes. DOX reduced rat cardiomyocytes viability in a time- and dose-dependent manner. DOX induced apoptosis in rat cardiomyocytes via activation of caspase-3. Cardiac function was significantly impaired by enhanced p38 activation. APS treatment reduced DOX-induced rat cardiomyocytes apoptosis by decreasing ROS production. To conclude, APS reduced DOX-induced cell apoptosis and ROS production by reduced activation of p38 signaling pathway.
authors.affiliation: Department of Critical Care Medicine, Yancheng City, No. 1 People's Hospital Yancheng, Jiangsu, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Critical Care Medicine, Yancheng City, No. 1 People's Hospital Yancheng, Jiangsu, China.
authors.forename: Lanping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Jinling Hospital Nanjing, 210002, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Yancheng City, No. 1 People's Hospital Yancheng, Jiangsu, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Deng
keywords: APS; DOX; ROS; cardiac cell apoptosis; p38 signaling