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Short-term exercise training attenuates acute doxorubicin cardiotoxicity

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Abstract

Doxorubicin (DOX) is a potent and widely used antineoplastic agent. Despite the efficacy of DOX, its clinical use is limited by a dose-dependent cardiotoxicity. Chronic exercise training has been shown to protect against DOX-induced cardiotoxicity. It is less clear whether short-term exercise can attenuate DOX-induced dysfunction. The purposes of this study were to determine if short-term wheel running and treadmill exercise training can attenuate the cardiac dysfunction that accompanies DOX treatment and to investigate possible mechanisms that may be involved with any protective effects of exercise. Male Sprague-Dawley rats engaged in a short-term 5-day voluntary wheel running (WR) or treadmill exercise (TM) regimen. Following the exercise preconditioning period, animals received either 10 or 15 mg/kg of DOX or an equivalent volume of saline (SAL). Five days after DOX/SAL exposure, cardiac function was examined. Western immunoblotting was used to quantify left ventricular sarcoendoplasmic reticulum calcium-ATPase 2a (SERCA2a) protein expression. Exercise preconditioning attenuated in vivo and ex vivo cardiac dysfunction observed with DOX treatment alone. Specifically, short-term treadmill exercise (TM + DOX10, 56 ± 4 %; TM + DOX15, 48 ± 5 %) and voluntary wheel running (WR + DOX10, 51 ± 5 %; WR + DOX15, 45 ± 3 %) consistently preserved fractional shortening when compared to sedentary (SED) animals treated with DOX (SED + DOX10, 48 ± 4 %; SED + DOX15, 39 ± 6 %). Likewise, both exercise protocols preserved left ventricular developed pressure (TM + DOX10, 115 ± 6 mmHg; TM + DOX15, 85 ± 5 mmHg; WR + DOX10, 92 ± 12 mmHg; WR + DOX15, 91 ± 8 mmHg) when compared to SED animals treated with DOX (SED + DOX10, 79 ± 6 mmHg; SED + DOX15, 69 ± 7 mmHg). SERCA2a expression was also preserved in TM + DOX and WR + DOX. These findings suggest that short-term exercise prior to DOX treatment may be a valuable adjuvant therapy to offset acute cardiotoxicities and that maintaining calcium handling in cardiomyocytes may be responsible, in part, for the preservation in cardiac function.

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Acknowledgments

This work was supported by funds provided by the University of Northern Colorado Sponsored Programs Office to Reid Hayward.

Conflict of interest

The authors do not have any conflicts of interest or professional relationships with companies or manufacturers who would benefit from the results of this study.

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Authors and Affiliations

  1. The Athletic Department, National Taiwan University, Taipei, Taiwan

    Chia-Ying Lien

  2. Department of Exercise and Rehabilitative Sciences, Slippery Rock University, Slippery Rock, PA, USA

    Brock T. Jensen

  3. School of Sport and Exercise Science and Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO, 80639, USA

    David S. Hydock & Reid Hayward

Authors
  1. Chia-Ying Lien
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  2. Brock T. Jensen
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  3. David S. Hydock
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  4. Reid Hayward
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Correspondence to Reid Hayward.

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Lien, CY., Jensen, B.T., Hydock, D.S. et al. Short-term exercise training attenuates acute doxorubicin cardiotoxicity. J Physiol Biochem 71, 669–678 (2015). https://doi.org/10.1007/s13105-015-0432-x

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  • DOI: https://doi.org/10.1007/s13105-015-0432-x

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