Ginkgolide B Exerts Cardioprotective Properties against Doxorubicin-Induced Cardiotoxicity by Regulating Reactive Oxygen Species, Akt and Calcium Signaling Pathways In Vitro and In Vivo

The aim of this study was to evaluate the effect of Ginkgolide B (GB) on doxorubicin (DOX) induced cardiotoxicity in vitro and in vivo. Rat cardiomyocyte cell line H9c2 was pretreated with GBand subsequently subjected to doxorubicin treatment. Cell viability and cell apopto- sis were assessed by MTT assay and Hoechst staining, respectively. Reactive oxygen spe- cies (ROS), Akt phosphorylation and intracellular calcium were equally determined in order to explore the underlying molecular mechanism. To verify the in vivo therapeutic effect of GB, we established a mouse model of cardiotoxicity and determined left ventricle ejection fraction (LVEF) and left ventricular mass (LVM). The in vitro experimental results indicated that pretreatment with GB significantly decreases the viability and apoptosis of H9c2 cells by decreasing ROS and intracellular calcium levels and activating Akt phosphorylation. In the in vivo study, we recorded an improved LVEF and a decreased LVM in the group of car- diotoxic rats treated with GB. Altogether, our findings anticipate that GBexerts a cardiopro- tective effect through possible regulation of the ROS, Akt and calcium pathways. The findings suggest that combination ofGB with DOX in chemotherapy could help avoid the cardiotoxic side effects of GB. Introduction