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Cardiovascular Research Advance Access originally published online on July 16, 2008
Cardiovascular Research 2008 80(2):227-235; doi:10.1093/cvr/cvn192
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes

Tsun-Jui Liu1,2,{dagger}, Yueh-Chiao Yeh1,{dagger}, Chih-Tai Ting1,2, Wen-Lieng Lee1,2, Li-Chuan Wang1, Hsiao-Wei Lee1, Kuo-Yang Wang1,3, Hui-Chun Lai4 and Hui-Chin Lai1,2,*

1 Cardiovascular Center, Taichung Veterans General Hospital, 160, Sec. 3, Taichungkang Road, Taichung 407, Taiwan, Republic of China
2 Department of Medicine, Surgery and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, Republic of China
3 Department of Medicine, Chung-Shan Medical University, Taichung, Taiwan, Republic of China
4 Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Linkoh, Taiwan, Republic of China

* Corresponding author. Tel: +886 4 23592525; fax: +886 4 23599257. E-mail address: 854k{at}vghtc.gov.tw; trliu{at}vghtc.gov.tw

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 µM), EGb761 (25 µg/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.

KEYWORDS Ginkgo; Doxorubicin; Apoptosis; p53; Cardiomyocyte


Time for primary review: 30 days

{dagger} Tsun-Jui Liu and Yueh-Chiao Yeh contributed equally to this paper.


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