Effects of Exercise on Doxorubicin Accumulation and Multidrug Resistance Protein Expression in Striated Muscle

1
David Hydock
David Hydock
2
Colin J Quinn
Colin J Quinn
3
Noah M. Gibson
Noah M. Gibson
4
Keith B. Pfannenstiel
Keith B. Pfannenstiel
5
Alex C. Bashore
Alex C. Bashore
6
Reid Hayward
Reid Hayward
7
David S. Hydock
David S. Hydock
1 University of Northern Colorado

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Effects of Exercise on Doxorubicin Accumulation and Multidrug Resistance Protein Expression in Striated Muscle Banner
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The chemotherapy drug doxorubicin (DOX) is well known to induce cardiac and skeletal muscle dysfunction. Previous studies demonstrate that exercise can mitigate dysfunction, reduce myocardial DOX accumulation, and depress markers of oxidative stress, but a putative mechanism is unknown. The aim of this study was to determine whether multidrug resistance protein (MRP) expression contributes to the protective effects of exercise against DOX-induced muscular dysfunction. Lower left ventricle (LV) and soleus DOX concentrations were observed in exercised animals, and MRP-1, MRP-2, and MRP-7 expression was significantly increased in the LV with exercise. No MRP variations were apparent in skeletal muscles following the exercise protocol. As a marker of oxidative stress, malondialdehyde+4 hydroxyalkenal levels were analyzed, and exercise reduced both cardiac and skeletal muscle levels from exercised trained animals treated with DOX had significantly lower levels than SED-DOX. This study suggests increased MRP expression with exercise may contribute to exercise-induced protection in cardiac muscle but not skeletal muscle.

33 Cites in Articles

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Funding

No external funding was declared for this work.

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

No ethics committee approval was required for this article type.

Data Availability

Not applicable for this article.

David Hydock. 2017. \u201cEffects of Exercise on Doxorubicin Accumulation and Multidrug Resistance Protein Expression in Striated Muscle\u201d. Global Journal of Medical Research - K: Interdisciplinary GJMR-K Volume 16 (GJMR Volume 16 Issue K6): .

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Crossref Journal DOI 10.17406/gjmra

Print ISSN 0975-5888

e-ISSN 2249-4618

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v1.2

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February 4, 2017

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The chemotherapy drug doxorubicin (DOX) is well known to induce cardiac and skeletal muscle dysfunction. Previous studies demonstrate that exercise can mitigate dysfunction, reduce myocardial DOX accumulation, and depress markers of oxidative stress, but a putative mechanism is unknown. The aim of this study was to determine whether multidrug resistance protein (MRP) expression contributes to the protective effects of exercise against DOX-induced muscular dysfunction. Lower left ventricle (LV) and soleus DOX concentrations were observed in exercised animals, and MRP-1, MRP-2, and MRP-7 expression was significantly increased in the LV with exercise. No MRP variations were apparent in skeletal muscles following the exercise protocol. As a marker of oxidative stress, malondialdehyde+4 hydroxyalkenal levels were analyzed, and exercise reduced both cardiac and skeletal muscle levels from exercised trained animals treated with DOX had significantly lower levels than SED-DOX. This study suggests increased MRP expression with exercise may contribute to exercise-induced protection in cardiac muscle but not skeletal muscle.

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Effects of Exercise on Doxorubicin Accumulation and Multidrug Resistance Protein Expression in Striated Muscle

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