title: Ginkgolide B Exerts Cardioprotective Properties against Doxorubicin-Induced Cardiotoxicity by Regulating Reactive Oxygen Species, Akt and Calcium Signaling Pathways In Vitro and In Vivo.
abstract: 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 GB and subsequently subjected to doxorubicin treatment. Cell viability and cell apoptosis were assessed by MTT assay and Hoechst staining, respectively. Reactive oxygen species (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 cardiotoxic rats treated with GB. Altogether, our findings anticipate that GB exerts a cardioprotective effect through possible regulation of the ROS, Akt and calcium pathways. The findings suggest that combination of GB with DOX in chemotherapy could help avoid the cardiotoxic side effects of GB.
authors.affiliation: Department of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Jianpu
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
authors.forename: Zongjun
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D066126:Cardiotoxicity / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival; D004317:Doxorubicin / Q000633:toxicity; D005343:Fibrinolytic Agents / Q000494:pharmacology; D046934:Ginkgolides / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D017382:Reactive Oxygen Species; D004317:Doxorubicin; C045856:ginkgolide B; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium