Mitochondrial accumulation of doxorubicin in cardiac and diaphragm muscle following exercise preconditioning

Doxorubicin (DOX) is a highly effective anthracycline antibiotic. Unfortunately, the clinical use of DOX is limited by the risk of deleterious effects to cardiac and respiratory (i.e. diaphragm) muscle, resulting from mitochondrial reactive oxygen species (ROS) production. In this regard, exercise is demonstrated to protect against DOX-induced myotoxicity and prevent mitochondrial dysfunction. However, the protective mechanisms are currently unclear. We hypothesized that exercise may induce protection by increasing the expression of mitochondria-specific ATP-binding cassette (ABC) transporters and reducing mitochondrial DOX accumulation. Our results confirm this finding and demonstrate that two weeks of exercise preconditioning is sufficient to prevent cardiorespiratory dysfunction.