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Exercise attenuates doxorubicin‐induced skeletal muscle damage
Author(s) -
Smuder Ashley J,
Min Kisuk,
Kavazis Andreas N
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.600.21
Subject(s) - skeletal muscle , doxorubicin , catalase , oxidative stress , superoxide dismutase , chemistry , pharmacology , lipid peroxidation , antioxidant , medicine , soleus muscle , myocyte , endocrinology , calpain , biochemistry , chemotherapy , enzyme
Doxorubicin (DOX) is an antitumor agent used in cancer treatment. However, DOX induces myocyte oxidative damage via increased free radical generation. In this regard, exercise presents a possible intervention for DOX toxicity through the induction of cytoprotective proteins. Therefore, we tested the hypothesis that DOX‐induced skeletal muscle damage could be attenuated by endurance exercise training. Sprague‐Dawley rats were randomly assigned to one of the following groups: sedentary, exercise, DOX, or exercise with DOX. Following the treatment protocol, soleus muscle was removed for subsequent analysis. Exercise prevented DOX induced increases in muscle lipid peroxidation. In addition, exercise training was sufficient in preventing muscle DOX induced HSP72 reduction. Furthermore, muscle levels of catalase, CuZn, and Mn‐superoxide dismutase increased with DOX suggesting antioxidant upregulation may act to combat increased oxidant production. Moreover, DOX resulted in increased muscle levels of ubiquitin‐protein conjugates as well as caspase‐3 and calpain I activity, all of which were attenuated with exercise training. These results suggest that DOX promotes skeletal muscle oxidative damage and protease activation. Importantly, exercise training appears to counteract the deleterious side effects of DOX. Supported by an AHA grant awarded to ANK.