Mitochondrial translocator protein (TSPO) ligands prevent doxorubicin-induced mechanical dysfunction and cell death in isolated cardiomyocytes

Contractile dysfunction and subsequent development of cardiomyopathies are well known limiting factors in the treatment of cancer with doxorubicin and have been linked to mitochondrial dysfunction. Here, using adult isolated paced cardiomyocytes, we have demonstrated that ligands of translocator pro...

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Bibliographic Details
Published in:Mitochondrion 2013-11, Vol.13 (6), p.688-697
Main Authors: de Tassigny, Alexandra d'Anglemont, Assaly, Rana, Schaller, Sophie, Pruss, Rebecca M, Berdeaux, Alain, Morin, Didier
Format: Article
Language:English
Subjects:
Animals
Biochemistry, Molecular Biology
Carrier Proteins - metabolism
Cell Death - drug effects
Doxorubicin - pharmacology
Life Sciences
Ligands
Mice
Mice, Knockout
Mitochondria, Heart - metabolism
Myocytes, Cardiac - cytology
Myocytes, Cardiac - drug effects
Reactive Oxygen Species - metabolism
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Summary:Contractile dysfunction and subsequent development of cardiomyopathies are well known limiting factors in the treatment of cancer with doxorubicin and have been linked to mitochondrial dysfunction. Here, using adult isolated paced cardiomyocytes, we have demonstrated that ligands of translocator protein (TSPO) 4'-chlorodiazepam and TRO40303 prevented the doxorubicin-induced alterations in contractility and improved cardiomyocyte viability. This cardioprotective effect was closely associated with both a potent reduction in reactive oxygen species production and inhibition of mitochondrial permeability transition pore opening. Thus, preventive administration of TSPO ligands may represent a novel pharmacological strategy to protect the heart during doxorubicin treatment.
ISSN:1567-7249
1872-8278
DOI:10.1016/j.mito.2013.10.001