AIMS: The objective of this study was to investigate whether a cytoprotective herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial effect on doxorubicin-induced cardiac toxicity in vitro and in vivo. METHODS AND RESULTS: Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 microM), EGb761 (25 microg/mL), or EGb761 plus doxorubicin. After 24 h, doxorubicin upregulated p53 mRNA expression, disturbed Bcl-2 family protein balance, disrupted mitochondrial membrane potential, precipitated mitochondrion-dependent apoptotic signalling, induced apoptotic cell death, and reduced viability of cardiomyocytes, whereas EGb761 pretreatment suppressed all the actions of doxorubicin. Similarly, rats treated with doxorubicin [3 mg/kg intraperitoneally (i.p.) three doses every other day] displayed retarded growth of body and heart as well as elevated apoptotic indexes in heart tissue at both 7 and 28 days after exposure, whereas EGb761 pretreatment (5 mg/kg i.p. 1 day before each dose of doxorubicin) effectively neutralized the aforementioned gross and cellular adverse effects of doxorubicin. CONCLUSION: Doxorubicin impairs viability of cardiomyocytes at least partially by activating the p53-mediated, mitochondrion-dependent apoptotic signalling. EGb761 can effectively and extensively counteract this action of doxorubicin, and may potentially protect the heart from the severe toxicity of doxorubicin.
AIMS: The objective of this study was to investigate whether a cytoprotective herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial effect on doxorubicin-induced cardiac toxicity in vitro and in vivo. METHODS AND RESULTS: Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 microM), EGb761 (25 microg/mL), or EGb761 plus doxorubicin. After 24 h, doxorubicin upregulated p53 mRNA expression, disturbed Bcl-2 family protein balance, disrupted mitochondrial membrane potential, precipitated mitochondrion-dependent apoptotic signalling, induced apoptotic cell death, and reduced viability of cardiomyocytes, whereas EGb761 pretreatment suppressed all the actions of doxorubicin. Similarly, rats treated with doxorubicin [3 mg/kg intraperitoneally (i.p.) three doses every other day] displayed retarded growth of body and heart as well as elevated apoptotic indexes in heart tissue at both 7 and 28 days after exposure, whereas EGb761 pretreatment (5 mg/kg i.p. 1 day before each dose of doxorubicin) effectively neutralized the aforementioned gross and cellular adverse effects of doxorubicin. CONCLUSION:Doxorubicin impairs viability of cardiomyocytes at least partially by activating the p53-mediated, mitochondrion-dependent apoptotic signalling. EGb761 can effectively and extensively counteract this action of doxorubicin, and may potentially protect the heart from the severe toxicity of doxorubicin.
Authors: Sandeep K Mallipattu; Sylvia J Horne; Vivette D'Agati; Goutham Narla; Ruijie Liu; Michael A Frohman; Kathleen Dickman; Edward Y Chen; Avi Ma'ayan; Agnieszka B Bialkowska; Amr M Ghaleb; Mandayam O Nandan; Mukesh K Jain; Ilse Daehn; Peter Y Chuang; Vincent W Yang; John C He Journal: J Clin Invest Date: 2015-02-17 Impact factor: 14.808
Authors: Rong Chang Chen; Xu Dong Xu; Xue Zhi Liu; Gui Bo Sun; Yin Di Zhu; Xi Dong; Jian Wang; Hai Jing Zhang; Qiang Zhang; Xiao Bo Sun Journal: Evid Based Complement Alternat Med Date: 2015-02-16 Impact factor: 2.629
Authors: Norma Serrano-García; José Pedraza-Chaverri; José Juan Mares-Sámano; Marisol Orozco-Ibarra; Arturo Cruz-Salgado; Anabel Jiménez-Anguiano; Julio Sotelo; Cristina Trejo-Solís Journal: Evid Based Complement Alternat Med Date: 2013-07-29 Impact factor: 2.629