Antioxidant treatment of hindlimb-unloaded mouse counteracts fiber type transition but not atrophy of disused muscles

Jean François Desaphy, Sabata Pierno, Antonella Liantonio, Viviana Giannuzzi, Claudio Digennaro, Maria Maddalena Dinardo, Giulia M. Camerino, Patrizia Ricciuti, Lorenza Brocca, Maria Antonietta Pellegrino, Roberto Bottinelli, Diana Conte Camerino

Research output: Contribution to journalArticle

Abstract

Oxidative stress was proposed as a trigger of muscle impairment in various muscle diseases. The hindlimb-unloaded (HU) rodent is a model of disuse inducing atrophy and slow-to-fast transition of postural muscles. Here, mice unloaded for 14 days were chronically treated with the selective antioxidant trolox. After HU, atrophy was more pronounced in the slow-twitch soleus muscle (Sol) than in the fast-twitch gastrocnemius and tibialis anterior muscles, and was absent in extensor digitorum longus muscle. In accord with the phenotype transition, HU Sol showed a reduced expression of myosin heavy chain type 2A (MHC-2A) and increase in MHC-2X and MHC-2B isoforms. In parallel, HU Sol displayed an increased sarcolemma chloride conductance related to an increased expression of ClC-1 channels, changes in excitability parameters, a positive shift of the mechanical threshold, and a decrease of the resting cytosolic calcium concentration. Moreover, the level of lipoperoxidation increased proportionally to the degree of atrophy of each muscle type. As expected, trolox treatment fully prevented oxidative stress in HU mice. Atrophy was not prevented but the drug significantly attenuated Sol phenotypic transition and excitability changes. Trolox treatment had no effect on control mice. These results suggest possible benefits of antioxidants in protecting muscle against disuse.

Original languageEnglish
Pages (from-to)553-563
Number of pages11
JournalPharmacological Research
Volume61
Issue number6
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Antioxidant
  • Muscle atrophy
  • Muscle excitability
  • Muscle plasticity
  • Oxidative stress
  • Sarcolemma chloride conductance

ASJC Scopus subject areas

  • Pharmacology

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