Antioxidant treatment of hindlimb-unloaded mouse counteracts fiber type transition but not atrophy of disused muscles.
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.
Desaphy
Jean-François
JF
Section of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Via Orabona 4 - campus, 70125 Bari, Italy.
Pierno
Sabata
S
Liantonio
Antonella
A
Giannuzzi
Viviana
V
Digennaro
Claudio
C
Dinardo
Maria Maddalena
MM
Camerino
Giulia M
GM
Ricciuti
Patrizia
P
Brocca
Lorenza
L
Pellegrino
Maria Antonietta
MA
Bottinelli
Roberto
R
Camerino
Diana Conte
DC
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000235:genetics; D002839:Chromans / Q000627:therapeutic use*; D019417:Hindlimb Suspension; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology*; D020966:Muscular Disorders, Atrophic / Q000188:drug therapy* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012508:Sarcolemma / Q000378:metabolism
D000975:Antioxidants; C086321:CLC-1 channel; D018118:Chloride Channels; D002839:Chromans; D012333:RNA, Messenger; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D002118:Calcium