Glucocorticoids are frequently used as anti-inflammatory and
immunosuppressive agents. However, high doses and/or prolonged use induce undesired secondary effects such as
muscular atrophy. Recently, de novo expression of
connexin43 and connexin45 hemichannels (
Cx43 HCs and Cx45 HCs, respectively) has been proposed to play a critical role in the mechanism underlying myofiber
atrophy induced by
dexamethasone (Dex: a synthetic
glucocorticoid), but their involvement in specific muscle changes promoted by Dex remains poorly understood. Moreover, treatments that could prevent the undesired effects of
glucocorticoids on skeletal muscles remain unknown. In the present work, a 7-day Dex treatment in adult mice was found to induce
weight loss and skeletal muscle changes including expression of functional
Cx43/Cx45 HCs, elevated atrogin immunoreactivity,
atrophy, oxidative stress and
mitochondrial dysfunction. All these undesired effects were absent in muscles of mice simultaneously treated with Dex and
vitamin E (VitE). Moreover, VitE was found to rapidly inhibit the activity of Cx HCs in freshly isolated myofibers of Dex treated mice. Exposure to alkaline pH induced
free radical generation only in HeLa cells expressing
Cx43 or Cx45 where Ca2+ was present in the extracellular milieu, response that was prevented by VitE. Besides, VitE and two other
anti-oxidant compounds,
Tempol and
Resveratrol, were found to inhibit
Cx43 HCs in HeLa cells transfectants. Thus, we propose that in addition to their intrinsic
anti-oxidant potency, some
antioxidants could be used to reduce expression and/or opening of Cx HCs and consequently reduce the undesired effect of
glucocorticoids on skeletal muscles.