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

Abstract

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.

• Authors: Alexandra d'Anglemont de Tassigny, Rana Assaly, Sophie Schaller, Rebecca M Pruss, Alain Berdeaux, Didier Morin
• Journal: Mitochondrion (Mitochondrion) Vol. 13 Issue 6 Pg. 688-97 (Nov 2013) ISSN: 1872-8278 [Electronic] Netherlands
• PMID: 24121045 (Publication Type: Journal Article)
• Copyright: © 2013.

Chemical References

• Carrier Proteins
• Ligands
• Reactive Oxygen Species
• Doxorubicin

Topics

• Animals
• Carrier Proteins (metabolism)
• Cell Death (drug effects)
• Doxorubicin (pharmacology)
• Ligands
• Mice
• Mice, Knockout
• Mitochondria, Heart (metabolism)
• Myocytes, Cardiac (cytology, drug effects)
• Reactive Oxygen Species (metabolism)