Acute Whole Body Exercise Increases the Availability of Doxorubicin in the Plasma Post-Injection

Doxorubicin (DOX) is one of the most widely used chemotherapeutic agents prescribed in the treatment of solid tumors and hematological malignancies and its cardiotoxic side effects are well documented. However, the effects of DOX on skeletal muscle are not well understood and recently our laboratory demonstrated that post-injection, skeletal muscle sequesters DOX out of the plasma, decreasing its availability at the tumour. Therefore, the purpose of the present study was to determine whether exercise performed 24 hours following the administration of DOX would result in an increase in the amount of DOX available in the plasma. Male Sprague-Dawley rats (n = 12) were injected intraperitoneally with a 4.5 mg/kg dose of Dox and then randomly assigned to either a control group (n=6, no exercise) or an exercise group (n=6). Twenty-four hours later the exercise group underwent a 60-minute swimming protocol and all animals were subsequently sacrificed and blood samples collected. There was is a significant increase in the plasma concentration of DOX (108±12 nM) post-exercise as compared to control (39±14 nM). In contrast, there were no significant differences between groups (Control = 10±3 nM, Exercise = 12±2 nM) in the plasma concentration of doxorubicinol (the breakdown and excretion product of DOX). These data clearly show that a single bout of whole body exercise results in elevated plasma DOX concentrations and it is postulated that the release of Dox from exercising muscle most likely accounts for this increase. These findings are also of clinical therapeutic importance as exercise may be used to increase the effectiveness of DOX in the chemotherapy treatment regimen.