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Exercise Protects Skeletal Muscle during Chronic Doxorubicin Administration

PURPOSETo assess the ability for exercise training performed before and during bi-weekly doxorubicin (DOX) administration to attenuate adverse effects of DOX on skeletal muscle. We hypothesized that DOX treatment would increase REDD1, impair mammalian target of rapamycin (mTOR) signaling, and reduce...

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Published in:Medicine and science in sports and exercise 2017-12, Vol.49 (12), p.2394-2403
Main Authors: Dickinson, Jared M, D’Lugos, Andrew C, Mahmood, Tara N, Ormsby, Jordan C, Salvo, Lara, Dedmon, W Logan, Patel, Shivam H, Katsma, Mark S, Mookadam, Farouk, Gonzales, Rayna J, Hale, Taben M, Carroll, Chad C, Angadi, Siddhartha S
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Language:English
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Summary:PURPOSETo assess the ability for exercise training performed before and during bi-weekly doxorubicin (DOX) administration to attenuate adverse effects of DOX on skeletal muscle. We hypothesized that DOX treatment would increase REDD1, impair mammalian target of rapamycin (mTOR) signaling, and reduce muscle fiber size, and that exercise training would attenuate these responses. METHODSEight-week old ovariectomized female Sprague-Dawley rats were randomized to one of four treatmentsExercise+DOX (Ex-Dox); Ex+Vehicle (Ex-Veh), Sedentary+DOX (Sed-Dox); and Sed+Veh (Sed-Veh). DOX (4mg/kg) or vehicle (saline) intraperitoneal injections were performed bi-weekly for a total of 3 injections (cumulative dose 12mg/kg). Ex animals performed interval exercise (4x4min, 85-90 %VO2peak) 5d/week starting one week prior to the first injection and continued throughout study duration. Animals were euthanized ~5d following the last injection, during which the soleus muscle was dissected and prepared for immunoblot and immunohistochemical analyses. RESULTSREDD1 mRNA and protein were increased only in Sed-Dox (P
ISSN:0195-9131
1530-0315
DOI:10.1249/MSS.0000000000001395