Effects of Exercise on Doxorubicin-Induced Skeletal Muscle Dysfunction

Chemotherapy treatment with doxorubicin (DOX) can have a negative effect on normal skeletal muscle function. Recent research demonstrates the potential value of exercise in alleviating DOX-induced cardiotoxicity. Yet up to now, little research has been done to examine whether exercise might also be effective in addressing DOX's skeletal muscle adverse effects, especially because posttreatment skeletal muscle dysfunction may cause patient difficulties with completing activities of daily living. The main aim of this study was to examine how resistance training (RT) and treadmill (TM) training play a role in preventing DOX-induced skeletal muscle dysfunction.

Male Sprague-Dawley rats were randomly placed into an RT, TM, or sedentary (SED) group for 10 wk and then received either a bolus injection of DOX (15 mg·kg) or saline as a control. Skeletal muscle function was then assessed ex vivo 5 d after injection.

SED animals treated with DOX showed significantly lower maximal twitch force, maximal rate of force production, and maximal rate of force decline versus SED + saline in the soleus (SOL) (Type I muscle). In the extensor digitorum longus (Type II muscle), treatment with DOX resulted in a significantly lower maximal rate of force production and maximal rate of force decline. RT preserved maximal twitch force and maximal rate of force decline in the SOL. TM attenuated DOX-induced fatigue in the SOL but not in the extensor digitorum longus.

These findings suggest that RT and TM before DOX could be useful in preserving skeletal muscle function and minimizing fatigue after chemotherapy, but this protection may be dependent on the skeletal muscle type.