Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes
Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes
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DOI：
10.1093/cvr/cvn192
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发表时间：
2008-11-01
影响因子：
10.8
通讯作者：
Lai, Hui-Chin
中科院分区：
文献类型：
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作者：
Liu, Tsun-Jui;Yeh, Yueh-Chiao;Lai, Hui-Chin
目的-本研究的目的是调查是否有一种细胞保护性草药衍生剂，银杏叶提取物（EGb）761，可以有一个有益的影响阿霉素诱导的心脏毒性在体外和体内。方法和结果原代培养的新生大鼠心肌细胞进行了治疗的车辆，阿霉素（1 μ M），EGb 761（25 μ g/mL），或EGb 761加阿霉素。24小时后，阿霉素上调p53 mRNA的表达，扰乱Bcl-2家族蛋白平衡，破坏线粒体膜电位，沉淀依赖于细胞凋亡信号，诱导凋亡细胞死亡，并降低心肌细胞的活力，而EGb 761预处理抑制阿霉素的所有行动。类似地，用多柔比星[3 mg/kg腹膜内（i. p.）每隔一天三次剂量]在暴露后7天和28天均显示身体和心脏生长迟缓以及心脏组织中细胞凋亡指数升高，而EGb 761预处理（每次多柔比星给药前1天，5 mg/kg i. p.）结论阿霉素至少部分地通过激活心肌细胞的细胞凋亡而损害心肌细胞的活力。p53介导的、依赖于p53的凋亡信号传导。EGb 761可以有效和广泛地抵消阿霉素的这种作用，并可能保护心脏免受阿霉素的严重毒性。
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 mu M), EGb761 (25 mu g/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.