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Article

Exercise, but Not Metformin Prevents Loss of Muscle Function Due to Doxorubicin in Mice Using an In Situ Method

1
Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USA
2
Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Manfredi Rizzo
Int. J. Mol. Sci. 2021, 22(17), 9163; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179163
Received: 28 July 2021 / Revised: 22 August 2021 / Accepted: 24 August 2021 / Published: 25 August 2021
(This article belongs to the Special Issue Molecular and Cellular Exercise Physiology in Metabolism)
Though effective in treating various types of cancer, the chemotherapeutic doxorubicin (DOX) is associated with skeletal muscle wasting and fatigue. The purpose of this study was to assess muscle function in situ following DOX administration in mice. Furthermore, pre-treatments with exercise (EX) or metformin (MET) were used in an attempt to preserve muscle function following DOX. Mice were assigned to the following groups: control, DOX, DOX + EX, or DOX + MET, and were given a single injection of DOX (15 mg/kg) or saline 3 days prior to sacrifice. Preceding the DOX injection, DOX + EX mice performed 60 min/day of running for 5 days, while DOX + MET mice received 5 daily oral doses of 500 mg/kg MET. Gastrocnemius–plantaris–soleus complex function was assessed in situ via direct stimulation of the sciatic nerve. DOX treatment increased time to half-relaxation following contractions, indicating impaired recovery (p < 0.05). Interestingly, EX prevented any increase in half-relaxation time, while MET did not. An impaired relaxation rate was associated with a reduction in SERCA1 protein content (p = 0.07) and AMPK phosphorylation (p < 0.05). There were no differences between groups in force production or mitochondrial respiration. These results suggest that EX, but not MET may be an effective strategy for the prevention of muscle fatigue following DOX administration in mice. View Full-Text
Keywords: skeletal muscle; chemotherapy; metformin; exercise; mitochondria; muscle contractions skeletal muscle; chemotherapy; metformin; exercise; mitochondria; muscle contractions
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MDPI and ACS Style

Mackay, A.D.; Marchant, E.D.; Louw, M.; Thomson, D.M.; Hancock, C.R. Exercise, but Not Metformin Prevents Loss of Muscle Function Due to Doxorubicin in Mice Using an In Situ Method. Int. J. Mol. Sci. 2021, 22, 9163. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179163

AMA Style

Mackay AD, Marchant ED, Louw M, Thomson DM, Hancock CR. Exercise, but Not Metformin Prevents Loss of Muscle Function Due to Doxorubicin in Mice Using an In Situ Method. International Journal of Molecular Sciences. 2021; 22(17):9163. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179163

Chicago/Turabian Style

Mackay, Amy D., Erik D. Marchant, Makensie Louw, David M. Thomson, and Chad R. Hancock 2021. "Exercise, but Not Metformin Prevents Loss of Muscle Function Due to Doxorubicin in Mice Using an In Situ Method" International Journal of Molecular Sciences 22, no. 17: 9163. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179163

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