Redox Regulation of Satellite Cells and Skeletal Muscle Healing

NCT03711838 | Completed

• 1 other identifier: Satellite Cells - UTH
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Satellite Cells; Redox Status; Exercise-induced Muscle Trauma; Aseptic Inflammation

Keywords

Pax7; MyoD; Antioxidants; Myogenic potential; Skeletal muscle healing

Outcome Measures

Primary Outcomes (7)

• Change in muscle satellite cells number (i.e. Pax7+ cells) and activation status (i.e. Pax7+/MyoD+ cells)

  Satellite cells number and activation status, will be assessed in muscle via immunohistochemistry.

  At baseline, before the exercise protocol and at days 2 and 8 following exercise.

• Change in muscle myogenic mRNA expression

  mRNA expression levels of Myogenic factor 5 (Myf5), myogenin and Myogenic factor 6 (Myf6/MRF4) and myostatin will be assessed in muscle using Real-Time Polymerase Chain Reaction (RT-PCR).

  At baseline, before the exercise protocol and at days 2 and 8 following exercise.

• Change in muscle inflammatory state

  Pro-inflammatory (M1+) and anti-inflammatory (M2+) macrophages will be measured in muscle using immunohistochemistry.

  At baseline, before the exercise protocol and at days 2 and 8 following exercise.

• Change in intracellular antioxidant enzymes in muscle

  Protein levels of Glutathione peroxidase 3 (GPx3), Superoxide dismutase 1 (SOD1) and Thioredoxin (Trx1) will be measured using western blotting.

  At baseline, before the exercise protocol and at days 2 and 8 following exercise.

• Change in muscle thiol content

  Concentration levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) will be measured spectophotometrically.

  At baseline, before the exercise protocol and at days 2 and 8 following exercise.

• Change in intracellular signaling proteins in muscle

  Protein levels of IGF-1, Notch1 and Wnt3 will be measured using western blotting.

  At baseline, before the exercise protocol and at days 2 and 8 following exercise.

• Change in skeletal muscle damage levels

  Skeletal muscle damage will be quantified via histochemistry using H\&E staining.

  At baseline, before the exercise protocol and at days 2 and 8 following exercise.

Secondary Outcomes (18)

• Resting metabolic rate (RMR)

  At baseline

• Body composition

  At baseline

• Maximal oxygen consumption (VO2max)

  At baseline

• Isokinetic strength

  At baseline, before the exercise protocol and at days 2 and 8 following exercise.

• Change in delayed onset of muscle soreness (DOMS)

  At baseline, before the exercise protocol and at days 2 and 8 following exercise.

Study Arms (2)

N-Acetylcysteine

EXPERIMENTAL

N-Acetylcysteine supplementation: Orally, 40 mg/kg per day in 3 doses (250 ml each) for 7 consecutive days and immediately post-exercise. The remaining 8 days, 40mg/kg per day in 3 doses (250 ml each).

Dietary Supplement: N-Acetylcysteine

Placebo

ACTIVE COMPARATOR

Placebo administration: Orally 750 ml per day in 3 doses (250 ml each) for 7 consecutive days and immediately post-exercise. The remaining 8 days, 750 ml per day in 3 doses (250 ml each).

Dietary Supplement: Placebo

Interventions

N-Acetylcysteine DIETARY_SUPPLEMENT

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.

N-Acetylcysteine

Placebo DIETARY_SUPPLEMENT

Placebo consisted of 248 ml water and 2 ml of natural, non-caloric, flavoring-sweetener containing sucralose.

Placebo

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• No recent history of musculoskeletal injury
• Non-smokers.
• Abstain from any vigorous physical activity during the study
• Abstain from consumption of caffeine, alcohol, performance-enhancing or antioxidant supplements, NSAIDs and medications before (at least 6 months) and during the study.

You may not qualify if:

• A known NAC intolerance or allergy
• A recent febrile illness
• A recent history of muscle lesion and/or lower limb trauma
• Presence of metabolic diseases
• Use of anti-inflammatory medication.
• Use of medication interacting with muscle metabolism.

Sponsors & Collaborators

• University of Thessaly: lead

Study Sites (1)

Laboratory of Exercise Biochemistry, Exercise Physiology,and Sports Nutrition, School of Physical Education and Sport Science, University of Thessaly

Trikala, Thessaly, 42100, Greece

Location

Related Publications (2)

• Papanikolaou K, Jamurtas AZ, Poulios A, Tsimeas P, Draganidis D, Margaritelis NV, Baloyiannis I, Papadopoulos C, Sovatzidis A, Deli CK, Rosvoglou A, Georgakouli K, Tzatzakis T, Nikolaidis MG, Fatouros IG. Skeletal muscle and erythrocyte redox status is associated with dietary cysteine intake and physical fitness in healthy young physically active men. Eur J Nutr. 2023 Jun;62(4):1767-1782. doi: 10.1007/s00394-023-03102-2. Epub 2023 Feb 24.

  PMID: 36828945 DERIVED

• Papanikolaou K, Draganidis D, Chatzinikolaou A, Laschou VC, Georgakouli K, Tsimeas P, Batrakoulis A, Deli CK, Jamurtas AZ, Fatouros IG. The redox-dependent regulation of satellite cells following aseptic muscle trauma (SpEED): study protocol for a randomized controlled trial. Trials. 2019 Jul 31;20(1):469. doi: 10.1186/s13063-019-3557-3.

  PMID: 31366396 DERIVED

MeSH Terms

Interventions

Acetylcysteine

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Konstantinos Papanikolaou, PhD

  University of Thessaly, School of Physical Education & Sport Science

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: October 19, 2018
• Study Start: July 22, 2019
• Primary Completion: May 1, 2022
• Study Completion: August 1, 2022
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

GR (1)