Doxorubicin (DOX) is known as an effective drug in the fight against various cancers. However, one of the greatest impediments is DOX-induced cardiomyopathy, which may potentially lead to heart failure. Accumulating evidence has shed light on the pathological mechanism of DOX-induced cardiotoxicity, but treatments to mitigate the cardiac damage are still required. In an attempt to address this issue, we evaluated whether exercise provides cardioprotective effects on the DOX-induced cardiotoxicity. We showed that treadmill exercise (3 times/week; 1-week of exercise acclimatization and 4-weeks of endurance exercise) during the DOX treatment successfully prevented the cardiac dysfunction. The DOX-stimulated expression of IκBα, NF-κB, COX-2, and IL-8 were all downregulated by exercise as well as the fibrosis factors (TGF-β1, phosphorylated ERK, Sp1, and CTGF). Moreover, we showed that treadmill exercise diminished the expression of several cardiac remodeling-associated factors, such as FGF2, uPA, MMP2, and MMP9. These results were in line with the finding that exercise intervention reduced cardiac fibrosis and restored cardiac function, with higher values of ejection fraction and fractional shortening compared to the DOX-treated group. Two commonly used indicators of cardiac injury, lactate dehydrogenase, and creatine kinase-MB, were also decreased in the exercise group. Collectively, our results suggested that it may be beneficial to prescribe treadmill exercise as an adjunct therapy to limit cardiac damage caused by DOX.

Background: Chemotherapy decreases fitness performance via repression of cardiopulmonary function and oxidative stress. This study was designed to investigate whether exercise intervention could improve exercises capacity and reduce systemic oxidative stress in patients with head and neck (H&N) cancer receiving chemotherapy. Methods: This is a single-center study. Forty-two H&N cancer patients who were undergoing chemotherapy were recruited in this study. An 8-week exercise intervention was performed by conducting the combination of aerobic and resistance exercise 3 days a week. The exercise training was conducted by a physiotherapist. The exercise capacity and exercise responses were measured from blood pressure (BP) and heart rate (HR). Oxidative stress markers from human plasma, such as total antioxidant capacity, 8-hydroxy-2-deoxyguanosine, malondialdehyde, and carbonyl content, were tested by activity kits. Results: We provide compelling evidence that exercise training ameliorated exercise responses and increased exercise capacity by repressing resting BP and increasing 1and 3-min BP recovery. We also found the resting HR was reduced, and the 1-and 3min HR recovery was increased after exercise training. In addition, the rating of perceived exertion after the peak exercise was reduced after exercise intervention. We also found that exercise training repressed oxidative stress markers by elevation of total antioxidant capacity and suppression of 8-OHd and carbonyl content in plasma. Discussion: We clearly demonstrate that exercise can promote exercise capacity and reduce oxidative stress in H&N cancer patients receiving chemotherapy, which might guide new therapeutic approaches for cancer patients, especially those undergoing chemotherapy.

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