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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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Autor principal: Kwon, Insu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 한국운동영양학회 2020
Materias:
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
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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.
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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
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