Resistance training attenuates decline in skeletal muscle function during doxorubicin treatment

While this is a pre-clinical study in rodents there are important implications for exercise medicine. Doxorubicin reduces muscle mass and strength however the relatively low intensity resistance training implemented prevented muscle loss and increased muscle strength.

Abstract

Previous research has shown that resistance training (RT) before doxorubicin (DOX) treatment attenuates the decline in muscle dysfunction; however, the effect of RT during DOX treatment is less known.

Purpose

Investigate the effects of RT before and during a 4-wk course of incremental DOX treatment on skeletal muscle function.

Methods

Male, Sprague-Dawley rats (N = 36) were randomly assigned to the following groups: sedentary+saline (SED + SAL), sedentary+DOX (SED + DOX), RT + SAL, or RT + DOX. The RT protocol utilized a raised cage model, which provided progressive hindlimb loading throughout the 14-wk study, whereas SED animals were kept in normal housing. Starting at week 10, DOX-treated animals received 3 mg·kg−1 DOX weekly for 4 wk (12 mg·kg−1 cumulative); whereas SAL-treated groups received 0.9% NaCl as a placebo. Grip strength was recorded at 0, 10, 12, and 14 wk. Ex vivo muscle function was performed on excised soleus (SOL) and extensor digitorum longus (EDL) from the right hind limb 5 d after the last injection and were analyzed for expression of creatine kinase (CK) and creatine transporters.

Results

SED + DOXtreated animals had significantly lower EDL mass compared with SED + SAL and RT + DOXtreated animals. Grip strength, EDL maximal force, and EDL force development were significantly lower in SED + DOXtreated animals compared with RT + SAL and SED + SAL. No significant differences in EDL function were found between RT + DOX and RT + SAL animals. DOX treatment reduced expression of CK in the SOL, which abated with RT.

Conclusions

Low-intensity RT may attenuate the decline in skeletal muscle function during incremental DOX treatment.

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