The role of resistance exercise on muscle atrophy induced by Dexamethasone

Abstract

Glucocorticoids has been used widely as treatment for allergy and inflammation, however, its chronic use determines several side effects such as insulin peripheral resistance, hyperglycemia and hyperinsulinemia, muscle glycogen reduction, hypertension, dyslipidemia, loss of body weight and muscle atrophy. Aerobic exercise training has been used to prevent and/or attenuate these diseases, however, its effects on muscle atrophy are still controversial. So, the resistance exercise has been recommended to attenuate the loss of muscle mass in some pathological conditions, although little is known about its effects on muscle atrophy induced by chronic treatment with dexamethasone (DEXA). The main objective of this work is to verify the preventive effect of resistance training at 80% of maximal capacity on the DEXA-induced muscle atrophy and the mechanisms responsible for this response. Wistar rats (200-250g) will be used and assigned in 4 groups: sedentary control (SC), sedentary treated with DEXA (SD), trained control (TC) and trained and treated with DEXA (TD). After an adaptation period on the ladder (5-7 days) they will perform a maximal test (1RM) for determine the intensity of the training. Then, the rats will be submitted to a resistance training (80% of maximum capacity, 4 days / week, 70 days) or kept sedentary. The 1RM tests will be performed at the beginning of the experimental protocol, after 4 and 8 weeks, as well as before and after treatment with DEXA. During the last 10 days of the experimental protocol, the animals will be treated with DEXA (Decadron®,0.5 mg / kg per day, i.p.), keeping their workouts regularly. The control animals will be treated with saline. The body weight will be measured weekly during the training period and daily during treatment. The fasting glycemia will be evaluated before the experimental protocol and before and after treatment with DEXA. After 48 hours of the last exercise session, the animals will be euthanized and the muscles, tibialis anterior (TA), soleus (SOL) and flexor hallucis longus (FHL) will be removed, cleaned and weighed immediately. The tibia will be used for normalization of muscle weights. The muscle samples will be homogenized, centrifuged and stored in a freezer at -80° C for proteins analysis. The Western blotting technique will be used to check the expression of the proteins P70S6, mTOR, FOXO-3a, Atrogin-1 and Murf. The results will be presented as average ± SEM. It will be used in 2 ways ANOVA with Tukey posthoc when there is interaction between the groups. The level of significance is 5%.