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Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner

Anthracycline chemotherapies are effective at reducing disease recurrence and mortality in cancer patients. However, these drugs also contribute to skeletal muscle wasting and dysfunction. The purpose of this study was to assess the impact of chronic doxorubicin (DOX) administration on satellite cel...

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Autores principales: D'Lugos, Andrew C., Fry, Christopher S., Ormsby, Jordan C., Sweeney, Kaylin R., Brightwell, Camille R., Hale, Taben M., Gonzales, Rayna J., Angadi, Siddhartha S., Carroll, Chad C., Dickinson, Jared M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453819/
https://www.ncbi.nlm.nih.gov/pubmed/30963722
http://dx.doi.org/10.14814/phy2.14052
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author D'Lugos, Andrew C.
Fry, Christopher S.
Ormsby, Jordan C.
Sweeney, Kaylin R.
Brightwell, Camille R.
Hale, Taben M.
Gonzales, Rayna J.
Angadi, Siddhartha S.
Carroll, Chad C.
Dickinson, Jared M.
author_facet D'Lugos, Andrew C.
Fry, Christopher S.
Ormsby, Jordan C.
Sweeney, Kaylin R.
Brightwell, Camille R.
Hale, Taben M.
Gonzales, Rayna J.
Angadi, Siddhartha S.
Carroll, Chad C.
Dickinson, Jared M.
author_sort D'Lugos, Andrew C.
collection PubMed
description Anthracycline chemotherapies are effective at reducing disease recurrence and mortality in cancer patients. However, these drugs also contribute to skeletal muscle wasting and dysfunction. The purpose of this study was to assess the impact of chronic doxorubicin (DOX) administration on satellite cell and capillary densities in different skeletal muscles. We hypothesized that DOX would reduce satellite cell and capillary densities of the soleus (SOL) and extensor digitorum longus (EDL) muscles, along with muscle fiber size. Ovariectomized female Sprague‐Dawley rats were randomized to receive three bi‐weekly intraperitoneal injections of DOX (4 mg∙kg(−1); cumulative dose 12 mg∙kg(−1)) or vehicle (VEH; saline). Animals were euthanized 5d following the last injection and the SOL and EDL were dissected and prepared for immunohistochemical and RT‐qPCR analyses. Relative to VEH, CSA of the SOL and EDL fibers were 26% and 33% smaller, respectively, in DOX (P < 0.05). In the SOL, satellite cell and capillary densities were 39% and 35% lower, respectively, in DOX (P < 0.05), whereas in the EDL satellite cell and capillary densities were unaffected by DOX administration (P > 0.05). Proliferating satellite cells were unaffected by DOX in the SOL (P > 0.05). In the SOL, MYF5 mRNA expression was increased in DOX (P < 0.05), while in the EDL MGF mRNA expression was reduced in DOX (P < 0.05). Chronic DOX administration is associated with reduced fiber size in the SOL and EDL; however, DOX appeared to reduce satellite cell and capillary densities only in the SOL. These findings highlight that therapeutic targets to protect skeletal muscle from DOX may vary across muscles.
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spelling pubmed-64538192019-04-19 Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner D'Lugos, Andrew C. Fry, Christopher S. Ormsby, Jordan C. Sweeney, Kaylin R. Brightwell, Camille R. Hale, Taben M. Gonzales, Rayna J. Angadi, Siddhartha S. Carroll, Chad C. Dickinson, Jared M. Physiol Rep Original Research Anthracycline chemotherapies are effective at reducing disease recurrence and mortality in cancer patients. However, these drugs also contribute to skeletal muscle wasting and dysfunction. The purpose of this study was to assess the impact of chronic doxorubicin (DOX) administration on satellite cell and capillary densities in different skeletal muscles. We hypothesized that DOX would reduce satellite cell and capillary densities of the soleus (SOL) and extensor digitorum longus (EDL) muscles, along with muscle fiber size. Ovariectomized female Sprague‐Dawley rats were randomized to receive three bi‐weekly intraperitoneal injections of DOX (4 mg∙kg(−1); cumulative dose 12 mg∙kg(−1)) or vehicle (VEH; saline). Animals were euthanized 5d following the last injection and the SOL and EDL were dissected and prepared for immunohistochemical and RT‐qPCR analyses. Relative to VEH, CSA of the SOL and EDL fibers were 26% and 33% smaller, respectively, in DOX (P < 0.05). In the SOL, satellite cell and capillary densities were 39% and 35% lower, respectively, in DOX (P < 0.05), whereas in the EDL satellite cell and capillary densities were unaffected by DOX administration (P > 0.05). Proliferating satellite cells were unaffected by DOX in the SOL (P > 0.05). In the SOL, MYF5 mRNA expression was increased in DOX (P < 0.05), while in the EDL MGF mRNA expression was reduced in DOX (P < 0.05). Chronic DOX administration is associated with reduced fiber size in the SOL and EDL; however, DOX appeared to reduce satellite cell and capillary densities only in the SOL. These findings highlight that therapeutic targets to protect skeletal muscle from DOX may vary across muscles. John Wiley and Sons Inc. 2019-04-08 /pmc/articles/PMC6453819/ /pubmed/30963722 http://dx.doi.org/10.14814/phy2.14052 Text en © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
D'Lugos, Andrew C.
Fry, Christopher S.
Ormsby, Jordan C.
Sweeney, Kaylin R.
Brightwell, Camille R.
Hale, Taben M.
Gonzales, Rayna J.
Angadi, Siddhartha S.
Carroll, Chad C.
Dickinson, Jared M.
Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner
title Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner
title_full Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner
title_fullStr Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner
title_full_unstemmed Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner
title_short Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner
title_sort chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle‐specific manner
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453819/
https://www.ncbi.nlm.nih.gov/pubmed/30963722
http://dx.doi.org/10.14814/phy2.14052
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