Resistance Exercise And Doxorubicin Treatment: Effects On Antioxidant Enzyme Expression In Type Ii Muscle

Abstract

Doxorubicin (DOX) is a chemotherapy drug used to effectively treat a variety of cancers. Its clinical use, however, is limited by its toxicities commonly attributed to increased oxidative stress in cardiac and skeletal muscle. The DOX-induced rise in oxidative stress can overwhelm endogenous antioxidants yet exercise (both endurance and resistance) has shown promise in attenuating this decline. Little information, however, is available on how DOX and resistance exercise affect antioxidant enzymes in type II skeletal muscle. PURPOSE: To determine the effects of resistance training before and during DOX treatment on superoxide dismutase (SOD) 1 and SOD2 expression in the primarily type II extensor digitorum longus (EDL) muscle. METHODS: Thirty-six male Sprague-Dawley rats were randomly assigned to one of four groups: sedentary+saline (SSS), sedentary+DOX (SSD), resistance training+saline (RRS), or resistance training+DOX (RRD). The resistance training protocol incorporated a raised cage model where food and water were elevated progressively which provided hind limb loading 10 weeks prior to DOX injection and 4 weeks during DOX treatment. Groups treated with DOX received 3 mg/kg DOX weekly for 4 weeks (12 mg/kg cumulative), and saline-treated groups received 0.9% NaCl as a placebo. Five days following the final DOX or saline injection, EDL muscles were excised, and Western blotting was performed to quantify SOD1 and SOD2 expression. RESULTS: Although no significant drug effects, activity effects, or drug x activity interactions were observed with SOD1 and SOD2 expression (P > 0.05), a trend toward SSD expressing less SOD1 and SOD2 than SSS was observed (-25% and -37%, respectively). This same trend in SOD1 and SOD2 expression, however, was not observed in RRD (+3% and -3%, respectively vs SSS). CONCLUSIONS: The DOX dosing regimen used in the current study had no effect on SOD1 and SOD2 expression in the EDL muscle, and the resistance training protocol also did not affect SOD1 and SOD2 expression. These results suggest that resistance exercise may play a limited role in modulating oxidative stress of DOX in type II skeletal muscle.