Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise

Michailidis, Yannis, Karagounis, Leonidas G, Terzis, Gerasimos, Jamurtas, Athanasios Z., Spengos, Kontantinos, Tsoukas, Dimitrios, Chatzinikolaou, Athanasios, Mandalidis, Dimitrios, Stefanetti, Renae J., Papassotiriou, Ioannis, Athanasopoulos, Spyros, Hawley, John A., Russell, Aaron P. and Fatouros, Ioannis G. 2013, Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise, American journal of clinical nutrition, vol. 98, no. 1, pp. 233-245, doi: 10.3945/ajcn.112.049163.

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Title Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise
Author(s) Michailidis, Yannis
Karagounis, Leonidas G
Terzis, Gerasimos
Jamurtas, Athanasios Z.
Spengos, Kontantinos
Tsoukas, Dimitrios
Chatzinikolaou, Athanasios
Mandalidis, Dimitrios
Stefanetti, Renae J.
Papassotiriou, Ioannis
Athanasopoulos, Spyros
Hawley, John A.
Russell, Aaron P.ORCID iD for Russell, Aaron P.
Fatouros, Ioannis G.
Journal name American journal of clinical nutrition
Volume number 98
Issue number 1
Start page 233
End page 245
Total pages 13
Publisher American Society for Nutrition
Place of publication Bethesda, Md.
Publication date 2013-07
ISSN 0002-9165
Keyword(s) Acetylcysteine
Adaptation, Physiological
C-Reactive Protein
Creatine Kinase
Cross-Over Studies
Dietary Supplements
Double-Blind Method
Muscle Contraction
NF-kappa B
Proto-Oncogene Proteins c-akt
Quadriceps Muscle
Ribosomal Protein S6
Ribosomal Protein S6 Kinases, 70-kDa
Signal Transduction
Sulfhydryl Compounds
Tumor Necrosis Factor-alpha
Young Adult
p38 Mitogen-Activated Protein Kinases
Science & Technology
Life Sciences & Biomedicine
Nutrition & Dietetics
Summary BACKGROUND: The major thiol-disulfide couple of reduced glutathione (GSH) and oxidized glutathione is a key regulator of major transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle after aseptic injury. Antioxidant supplementation may hamper exercise-induced cellular adaptations.
OBJECTIVE: The objective was to examine how thiol-based antioxidant supplementation affects skeletal muscle's performance and redox-sensitive signaling during the inflammatory and repair phases associated with exercise-induced microtrauma.
DESIGN: In a double-blind, crossover design, 10 men received placebo or N-acetylcysteine (NAC; 20 mg · kg(-1) · d(-1)) after muscle-damaging exercise (300 eccentric contractions). In each trial, muscle performance was measured at baseline, after exercise, 2 h after exercise, and daily for 8 consecutive days. Muscle biopsy samples from vastus lateralis and blood samples were collected before exercise and 2 h, 2 d, and 8 d after exercise.
RESULTS: NAC attenuated the elevation of inflammatory markers of muscle damage (creatine kinase activity, C-reactive protein, proinflammatory cytokines), nuclear factor κB phosphorylation, and the decrease in strength during the first 2 d of recovery. NAC also blunted the increase in phosphorylation of protein kinase B, mammalian target of rapamycin, p70 ribosomal S6 kinase, ribosomal protein S6, and mitogen activated protein kinase p38 at 2 and 8 d after exercise. NAC also abolished the increase in myogenic determination factor and reduced tumor necrosis factor-α 8 d after exercise. Performance was completely recovered only in the placebo group.
CONCLUSION: Although thiol-based antioxidant supplementation enhances GSH availability in skeletal muscle, it disrupts the skeletal muscle inflammatory response and repair capability, potentially because of a blunted activation of redox-sensitive signaling pathways. This trial was registered at as NCT01778309.
Language eng
DOI 10.3945/ajcn.112.049163
Field of Research 0 Not Applicable
Socio Economic Objective 0 Not Applicable
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2013, American Society for Nutrition
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