Early moderate intensity aerobic exercise intervention prevents doxorubicin-caused cardiac dysfunction through inhibition of cardiac fibrosis and inflammation

Hsin Lun Yang, Pei Ling Hsieh, Ching Hsia Hung, Hui Ching Cheng, Wan Ching Chou, Pei Ming Chu, Yun Ching Chang, Kun Ling Tsai

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number1102
JournalCancers
Volume12
Issue number5
DOIs
Publication statusPublished - 2020 May

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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