The Effects of Exercise on Antioxidants in Doxorubicin Treated Type 2 Muscle

Abstract

Doxorubicin (DOX) is an effective chemotherapy treatment that is associated with a number of deleterious side effects such as myotoxicity. Exercise has been shown previously to minimize this side effect and preserve skeletal muscle function. The protective effects of exercise on DOX-induced muscle dysfunction has been primarily studied in type I muscle, and as such, there is a lack of understanding of this exercise-induced protection in type II muscle. Exercise has been shown to preserve maximal twitch force in type 2 muscle from animals treated with DOX. In type 1 muscle, it is believed that exercise increases key antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) which help to attenuate the DOX-induced dysfunction. Understanding how exercise affects antioxidants in type 2 muscle treated with DOX could lead to a better understanding of the mechanisms behind Dox and exercise-induced myoprotection. PURPOSE: To investigate the effects of chronic treadmill (TM) and resistance training (RT) on antioxidant expression in type 2 skeletal muscle from rats receiving DOX. METHODS: Male Sprague–Dawley rats were randomly assigned to a TM, RT, or sedentary (SED) group for 10 weeks. At the end of the 10 week period, animals received a bolus DOX dose of 10 mg/kg, 12.5 mg/kg, or 15 mg/kg. Three days after injection, extensor digitorum longus (EDL) muscles were excised and analyzed for SOD1, GPX, and CAT expression using Western immunoblotting. RESULTS: No significant differences were found among groups regardless of DOX dose or exercise condition. GPX was on average 54.4% higher in TM+DOX groups and 71.9% higher in the RT+DOX groups when compared to those in the SED+DOX groups. SOD1 was on average 54.5% to 70.2% more prolific among the TM+DOX and RT+DOX groups. CAT content was on average 72.7.9%-73.3% more common among the TM+DOX and RT+DOX groups. CONCLUSION: The results of this study indicate that exercise-induced protection against DOX dysfunction in type 2 muscles is not necessarily due to alterations in SOD1, GPX, or CAT. There are likely other mechanisms that contribute to this myoprotection in type 2 skeletal muscle that warrant further investigation.