Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes
TJ Liu, YC Yeh, CT Ting, WL Lee… - Cardiovascular …, 2008 - academic.oup.com
Cardiovascular Research, 2008•academic.oup.com
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 …
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 …
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.
Oxford University Press