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Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice
[PURPOSE]: Doxorubicin (DOX) is a potent anti-cancer drug that appears to have severe myotoxicity due to accumulation. The skeletal muscle has a regeneration capacity through satellite cell activation when exposed to extracellular stimulus or damage. Endurance exercise (EXE) is a therapeutic strateg...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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한국운동영양학회
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451836/ https://www.ncbi.nlm.nih.gov/pubmed/32698257 http://dx.doi.org/10.20463/pan.2020.0010 |
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author | Kwon, Insu |
author_facet | Kwon, Insu |
author_sort | Kwon, Insu |
collection | PubMed |
description | [PURPOSE]: Doxorubicin (DOX) is a potent anti-cancer drug that appears to have severe myotoxicity due to accumulation. The skeletal muscle has a regeneration capacity through satellite cell activation when exposed to extracellular stimulus or damage. Endurance exercise (EXE) is a therapeutic strategy that improves pathological features and contributes to muscle homeostasis. Thus, this study investigated the effect of EXE training in mitigating chronic DOX-induced myotoxicity. [METHODS]: Male C57BL/6J mice were housed and allowed to acclimatize with free access to food and water. All the mice were randomly divided into four groups: sedentary control (CON, n=9), exercise training (EXE, n=9), doxorubicin treatment (DOX, n=9), doxorubicin treatment and exercise training (DOX+EXE, n=9) groups. The animals were intraperitoneally injected with 5 mg/kg/week of DOX treatment for 4 weeks, and EXE training was initiated for treadmill adaptation for 1 week and then performed for 4 weeks. Both sides of the soleus (SOL) muscle tissues were dissected and weighed after 24 hours of the last training sessions. [RESULTS]: DOX chemotherapy induced an abnormal myofiber’s phenotype and transition of myosin heavy chain (MHC) isoforms. The paired box 7 (PAX7) and myoblast determination protein 1 (MYOD) protein levels were triggered by DOX, while no alterations were shown for the myogenin (MYOG). DOX remarkably impaired the a-actinin (ACTN) protein, but the EXE training seems to repair it. DOX-induced myotoxicity stimulated the expression of the forkhead box O3 (FOXO3a) protein, which was accurately controlled and adjusted by the EXE training. However, the FOXO3a-mediated downstream markers were not associated with DOX and EXE. [CONCLUSION]: EXE postconditioning provides protective effects against chronic DOX-induced myotoxicity, and should be recommended to alleviate cancer chemotherapy-induced late-onset myotoxicity. |
format | Online Article Text |
id | pubmed-7451836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | 한국운동영양학회 |
record_format | MEDLINE/PubMed |
spelling | pubmed-74518362020-09-01 Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice Kwon, Insu Phys Act Nutr Original Articles [PURPOSE]: Doxorubicin (DOX) is a potent anti-cancer drug that appears to have severe myotoxicity due to accumulation. The skeletal muscle has a regeneration capacity through satellite cell activation when exposed to extracellular stimulus or damage. Endurance exercise (EXE) is a therapeutic strategy that improves pathological features and contributes to muscle homeostasis. Thus, this study investigated the effect of EXE training in mitigating chronic DOX-induced myotoxicity. [METHODS]: Male C57BL/6J mice were housed and allowed to acclimatize with free access to food and water. All the mice were randomly divided into four groups: sedentary control (CON, n=9), exercise training (EXE, n=9), doxorubicin treatment (DOX, n=9), doxorubicin treatment and exercise training (DOX+EXE, n=9) groups. The animals were intraperitoneally injected with 5 mg/kg/week of DOX treatment for 4 weeks, and EXE training was initiated for treadmill adaptation for 1 week and then performed for 4 weeks. Both sides of the soleus (SOL) muscle tissues were dissected and weighed after 24 hours of the last training sessions. [RESULTS]: DOX chemotherapy induced an abnormal myofiber’s phenotype and transition of myosin heavy chain (MHC) isoforms. The paired box 7 (PAX7) and myoblast determination protein 1 (MYOD) protein levels were triggered by DOX, while no alterations were shown for the myogenin (MYOG). DOX remarkably impaired the a-actinin (ACTN) protein, but the EXE training seems to repair it. DOX-induced myotoxicity stimulated the expression of the forkhead box O3 (FOXO3a) protein, which was accurately controlled and adjusted by the EXE training. However, the FOXO3a-mediated downstream markers were not associated with DOX and EXE. [CONCLUSION]: EXE postconditioning provides protective effects against chronic DOX-induced myotoxicity, and should be recommended to alleviate cancer chemotherapy-induced late-onset myotoxicity. 한국운동영양학회 2020-06-30 /pmc/articles/PMC7451836/ /pubmed/32698257 http://dx.doi.org/10.20463/pan.2020.0010 Text en ©2020 The Korean Society for Exercise Nutrition ©2020 Insu Kwon.; Licence Physical Activity and Nutrition. This is an open access article distributed under the terms of the creative commons attribution license (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the orginal work is properly cited. |
spellingShingle | Original Articles Kwon, Insu Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice |
title | Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice |
title_full | Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice |
title_fullStr | Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice |
title_full_unstemmed | Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice |
title_short | Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice |
title_sort | protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451836/ https://www.ncbi.nlm.nih.gov/pubmed/32698257 http://dx.doi.org/10.20463/pan.2020.0010 |
work_keys_str_mv | AT kwoninsu protectiveeffectsofenduranceexerciseonskeletalmuscleremodelingagainstdoxorubicininducedmyotoxicityinmice |