Redox Regulation of Satellite Cells and Skeletal Muscle Healing
Condition: Satellite Cells; Redox Status; Exercise-induced Muscle Trauma; Aseptic Inflammation
MeSH terms: Inflammation
Study type: Interventional

Summary: 
      Skeletal muscle stem cells (Satellite cells) are indispensable for muscle growth and
      remodeling following myofibril damage. Skeletal muscle trauma is present in numerous
      catabolic conditions, characterized by elevated proteolysis and muscle wasting such as,
      cancer cachexia and muscular dystrophy, which result in physical capacity impairment and a
      deteriorated quality of life. Recent studies performed in animals and cell cultures indicate
      that the increased levels of inflammation and oxidative stress and the reduction of
      antioxidant defense may blunt the satellite cells response and myogenic programming during
      muscle healing. However, evidence regarding the effects of redox status on satellite cells
      and muscle myogenic potential in humans is lacking. Exercise-induced muscle damage bears
      striking similarities with the aforementioned conditions, which makes it a valuable tool to
      investigate the redox-dependent regulation of satellite cells during muscle healing. Thus,
      the objectives of the present study are to examine the effects of redox status perturbation
      (via N-acetylcysteine administration) on intracellular pathways responsible for satellite
      cells responses at rest and following aseptic muscle trauma induced by damaging exercise.
    

Detailed description: 
      A total number of 40-60 males, young individuals aged 18-30 years, will be initially enrolled
      in the study. Then, participants will be allocated to either a 1) Low Respondents (LR) or a
      2) High Respondents (HR) group based on the basal satellite cells content of their vastus
      lateralis muscle of their dominant leg. In a double-blind, crossover, repeated measures
      design, participants will consume either Placebo (PLA) or N-acetylcysteine (NAC) before
      (7-day loading phase), on exercise day and for 8 consecutive days following a single bout of
      intense exercise (300 eccentric contractions at 30 deg/sec in an isokinetic dynamometer). In
      both conditions, blood samples and muscle biopsies will be collected at baseline, before the
      exercise protocol and at 2- and 8-days post-exercise. Muscle performance and soreness will
      also be assessed at the same time points. Before the first trial, participants' dietary
      intake (via diet recalls) and physical activity (via accelerometry) will be analyzed and
      nutritional plans will be provided to participants in order to normalize their antioxidant
      and protein intake. A 4-week washout period will be implemented between trials. Blood samples
      will be analyzed for inflammation and oxidative stress markers. Muscle samples will be
      analyzed for satellite cells responses and myogenic potential, protein levels of
      intracellular signaling proteins, muscle thiols and antioxidant enzymes activity.
    

Intervention name(s): N-Acetylcysteine; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): N-Acetylcysteine in a powder form diluted in a 250 ml drink containing 248 ml water and 2 ml of natural, non-caloric, flavoring-sweetener containing sucralose.; Placebo consisted of 248 ml water and 2 ml of natural, non-caloric, flavoring-sweetener containing sucralose.
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Pax7; MyoD; Antioxidants; Myogenic potential; Skeletal muscle healing