摘要

Chemotherapy-induced cardiotoxicity has reportedly restricted the clinical application of drugs. However, the potential for astragalus polysaccharides (APS) to ameliorate 5-FU-induced cardiotoxicity remains largely unknown. In the present study, an MTT assay was applied to determine whether 5-FU affected cardiomyocyte viability. For in vivo study, the SD rats were randomly divided into three groups by direct gastric gavage for 7 days: Group I: saline group; Group II: 5-FU (1 mg/Kg body weight); and Group III: 5-FU+APS (1.5 g/kg body weight). The in vivo effects of 5-FU on cardiac function were explored through echocardiography. The SOD and MDA contents were also determined. We found that 5-FU significantly enhanced ROS production in primary cardiomyocytes in a dose-dependent manner. Primary cardiomyocytes viability was decreased by 5-FU in a dose-and time-dependent manner. 5-FU significantly enhanced the activation of caspase3, thereby prompting cardiomyocyte apoptosis. In addition, treatment with 5-FU obviously reduced the SOD content and enhanced the MDA level. Preincubation with APS could partially reverse 5-FU-induced SOD reduction and MDA upregulation. Western blot analysis demonstrated that treatment with APS decreased 5-FU-induced activation of caspase3 and reduced the expression of Bax. In conclusion, treatment with APS was shown to suppress 5-FU-induced cardiomyocyte apoptosis primarily by suppression of ROS production.