Análise temporal dos efeitos preventivos do exercício resistido sobre a atrofia muscular induzida por dexametasona
Resumo
Synthetic glucocorticoids have potent anti-inflammatory and immunosuppressive action, though its chronic usage can trigger muscle atrophy. On the other hand the resistance training (RT) acts in opposition to atrophic situations, although its effects on muscle atrophy induced by treatment with dexamethasone (DEX) are poorly known.The purpose of this study was to determine how long RT is required to promote preventive effects in flexor halluces longus (FHL) muscle atrophy induced by dexamethasone (DEX). After maximal voluntary carrying capacity (MVCC), 100 rats were separated in sedentary (SED) or resistance trained for 10 (RT10), 40 (RT40), 70 (RT70) and 100 (RT100) days. Groups were divided as control (CTRL) or treated with DEX. RT was performed with 80% of maximal voluntary carrying capacity (MVCC). During the last 10 days, the animals either received DEX (0.5 mg/kg/day, i.p.) or vehicle (saline, same volume as DEX treatment, i.p.). The FHL muscle was removed, cleaned, weighed and stored for determining the cross-sectional area, proteassomal activity 26s, and total p70S6K, p-p70S6KThr389, MuRF1, REDD1 and GAPDH protein level. The results arepresented as mean ± SEM. The repeated measures two-way analysis of variance (ANOVA) were used for food intake and, for further analysis,it was used two-way ANOVA, both with Tukey post hoc test and significance levelset as α<0.05. DEX reduced FHL mass (-26%), but RT70 and RT100 DEX groups presented atrophy attenuation. DEX reduced proteasome activity in SED (-33%) and RT70 (-44%) DEX. RT70 CTRL had increased proteasome activity when compared with RT10 and RT40 CTRL (+48% and +51%, respectively) groups and RT100 CTRL had reduced activity (-56%). DEX reduced phospho-p70S6KThr389/total p70S6k ratio in SED DEX (-24%), but it was reverted in RT10 (+48%) and RT70 DEX(+70%). RT70 CTRL presented higher values of this ratio than SED, RT40 and RT100 CTRL groups. DEX increased REDD1 (+47%) protein level only in SED DEX. MuRF-1 protein level increased in SED(+50%), RT10 (+45%) and RT40 (+46%)DEX groups, but it was blocked in RT70 and RT100 DEX groups. In summary, we suggest that DEX-induced FHL muscle atrophy requires at least 70 days of RT to be attenuated and this response involves a complete blockade of MuRF-1 and REDD1 protein level increase and the blockade phospho-p70S6KThr389/total p70S6k ratio reduction. Also, 100 days of RT did not promote any additional effects. It is interesting to note that only 10 days of RT evoked improvements in the synthesis pathway, which suggest that some molecular adjustments are required in early stages of skeletal muscle mass maintenance.