High-intensity exercise induces oxidative stress and inflammatory events in muscles.
Tumor necrosis factor (TNF)-α may alter muscle protein metabolism or promote muscle
regeneration. We hypothesized that a program of noninvasive chronic inspiratory loading
of different intensities induces a differential pattern of physiological, molecular,
and cellular events within rat diaphragms. Antioxidants and TNF-α blockade may influence
those events. In the diaphragm, gastrocnemius, and blood of rats exposed to high-intensity
inspiratory threshold loads (2 hour every 24 hours for 14 days), with and without
treatment with N-acetyl cysteine or infliximab (anti-TNF-α antibody), inflammatory
cells and cytokines, superoxide anion production, myogenesis markers, and muscle structure
were explored. In all animals, maximum inspiratory pressure (MIP) and body weight
were determined. High-intensity inspiratory loading for 2 weeks caused a decline in
MIP and body weight, and in the diaphragm induced a reduction in fast-twitch fiber
proportions and sizes, whereas inflammatory cells and cytokine levels, including TNF-α
immunohistochemical expression, superoxide anion, internal nuclei counts, and markers
of myogenesis were increased. Blockade of TNF-α improved respiratory muscle function
and structure, and animal weight, and, in the diaphragm, reduced inflammatory cell
numbers and superoxide anion production drastically while inducing larger increases
in protein and messenger RNA levels and immunohistochemical expression of TNF-α, internal
nuclei, and markers of muscle regeneration. Blunting of TNF-α also induced a reduction
in blood inflammatory cytokines and superoxide anion production. We conclude that
TNF-α synthesized by inflammatory cells or myofibers could have differential effects
on muscle structure and function in response to chronic, noninvasive, high-intensity
inspiratory threshold loading.
Abbreviations:
COPD (chronic obstructive pulmonary disease), ELISA (enzyme-linked immunosorbent assay), IL (interleukin), m-cadherin (muscle calcium-dependent cell adhesion), MIP (maximal inspiratory pressure), mRNA (messenger RNA), myf-6 (myogenic factor 6), MyHC (myosin heavy chain), NAC (N-acetylcysteine), TNF (Tumor necrosis factor)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 12, 2013
Accepted:
December 3,
2013
Received in revised form:
November 29,
2013
Received:
May 29,
2013
Identification
Copyright
© 2014 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
