title: Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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 clinicaltrials.gov as NCT01778309.
authors.affiliation: Democritus University of Thrace, Department of Physical Education and Sport Sciences, Komotini, Greece.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Michailidis
authors.forename: Leonidas G
authors.initials: LG
authors.lastname: Karagounis
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Terzis
authors.forename: Athanasios Z
authors.initials: AZ
authors.lastname: Jamurtas
authors.forename: Kontantinos
authors.initials: K
authors.lastname: Spengos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsoukas
authors.forename: Athanasios
authors.initials: A
authors.lastname: Chatzinikolaou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mandalidis
authors.forename: Renae J
authors.initials: RJ
authors.lastname: Stefanetti
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papassotiriou
authors.forename: Spyros
authors.initials: S
authors.lastname: Athanasopoulos
authors.forename: John A
authors.initials: JA
authors.lastname: Hawley
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
authors.forename: Ioannis G
authors.initials: IG
authors.lastname: Fatouros
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage; D000222:Adaptation, Physiological / Q000187:drug effects; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism; D004032:Diet; D019587:Dietary Supplements; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052097:Quadriceps Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D016328:NF-kappa B; D038601:Ribosomal Protein S6; D013438:Sulfhydryl Compounds; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048051:p38 Mitogen-Activated Protein Kinases; D003402:Creatine Kinase; D005978:Glutathione; D000111:Acetylcysteine