Exercise and Doxorubicin Modify Markers of Iron Overload and Cardiolipin Deficiency in Cardiac Mitochondria.

Doxorubicin (DOX) is a chemotherapeutic agent highly effective at limiting cancer progression. Despite the efficacy of this anticancer drug, the clinical use of DOX is limited due to cardiotoxicity. The cardiac mitochondria are implicated as the primary target of DOX, resulting in inactivation of electron transport system complexes, oxidative stress, and iron overload. However, it is established that the cardiac mitochondrial subpopulations reveal differential responses to DOX exposure, with subsarcolemmal (SS) mitochondria demonstrating redox imbalance and the intermyofibrillar (IMF) mitochondria showing reduced respiration. In this regard, exercise training is an effective intervention to prevent DOX-induced cardiac dysfunction. Although it is clear that exercise confers mitochondrial protection, it is currently unknown if exercise training mitigates DOX cardiac mitochondrial toxicity by promoting beneficial adaptations to both the SS and IMF mitochondria. To test this, SS and IMF mitochondria were isolated from sedentary and exercise-preconditioned female Sprague Dawley rats exposed to acute DOX treatment. Our findings reveal a greater effect of exercise preconditioning on redox balance and iron handling in the SS mitochondria of DOX-treated rats compared to IMF, with rescue of cardiolipin synthase 1 expression in both subpopulations. These results demonstrate that exercise preconditioning improves mitochondrial homeostasis when combined with DOX treatment, and that the SS mitochondria display greater protection compared to the IMF mitochondria. These data provide important insights into the molecular mechanisms that are in part responsible for exercise-induced protection against DOX toxicity.

The impact of low-intensity blood flow restriction endurance training on aerobic capacity, hemodynamics, and arterial stiffness.

BACKGROUND: The aim of this study was to determine the effects of short-term low-intensity blood flow restriction (BFR) endurance training (ET) programs on measures of aerobic capacity, hemodynamics, and arterial stiffness in healthy young males. METHODS: Thirty-nine healthy young recreationally active males participated in this short-term training study. They were randomly assigned to a high-intensity (HI; N.=11; trained at 60-70% of VO2 reserve [VO2R]), low-intensity (LI; N.=8; trained at 30-40% of VO2R), low-intensity with BFR (LI-BFR; N.=10; trained at 30-40% of VO2R with BFR) or a non-exercising control group (N.=10). The exercising subjects completed a 6-wk training protocol on a treadmill. Assessment of aerobic capacity (VO2max), hemodynamics and arterial stiffness were done before and after training. RESULTS: Statistical analyses revealed a significant condition main effect (P<0.05) for VO2max, indicating significant increase (P<0.05) in VO2max in LI-BFR group compared to control. There were no significant changes for resting heart rate (RHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), carotid-radial pulse wave velocity (PWV), and carotid-femoral PWV (P>0.05). However, femoral-tibial PWV decreased significantly (P<0.05) from baseline to post-training. CONCLUSIONS: The results indicate that the application of BFR during ET may cause faster and/or greater adaptations in one or more physiological systems resulting in improved cardiorespiratory fitness.