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

Cardiovasc Res. 2008 Nov 1;80(2):227-35. doi: 10.1093/cvr/cvn192. Epub 2008 Jul 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Cardiovascular Agents / pharmacology*
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytochromes c / metabolism
  • Cytoprotection
  • Disease Models, Animal
  • Doxorubicin
  • Heart Diseases / chemically induced
  • Heart Diseases / metabolism
  • Heart Diseases / pathology
  • Heart Diseases / prevention & control*
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / enzymology
  • Mitochondria, Heart / pathology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / pathology
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cardiovascular Agents
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Ginkgo biloba extract
  • Doxorubicin
  • Cytochromes c
  • Casp3 protein, rat
  • Caspase 3