Related Experiment Video
Updated: Feb 4, 2026
Tibial Nerve Transection - A Standardized Model for Denervation-induced Skeletal Muscle Atrophy in Mice
Published on: November 3, 2013
Skeletal Muscle Cell Oxidative Stress as a Possible Therapeutic Target in a Denervation-Induced Experimental
Hideyuki Kinoshita1, Sumihisa Orita1, Kazuhide Inage1
1Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Study Design:
A basic study using a rodent model of sarcopenia.
Objective:
To elucidate the contribution of oxidative stress to muscle degeneration and the efficacy of antioxidant treatment for sarcopenia using an animal model of neurogenic sarcopenia.
Summary Of Background Data:
Oxidative stress has been reported to be involved in a number of pathologies, including musculoskeletal disorders. Its relationship with sarcopenia, one of the potential origins of lower back pain, however, is not yet fully understood.
Methods:
Myoblast cell lines (C2C12) were treated with H2O2, an oxidative stress inducer, and N-acetyl-L-cysteine (NAC), an antioxidant. Apoptotic effects induced by oxidative stress and the antioxidant effects of NAC were assessed by western blotting, immunocytochemistry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays. An animal model of sarcopenia was produced via axotomy of the sciatic nerves to induce muscle atrophy. Twenty-four male Sprague-Dawley rats were divided into sham, sham+NAC, axotomy, and axotomy+NAC groups. Rats were provided water only or water containing NAC (1 g/L) for 4 weeks. The gastrocnemius muscle was isolated and stained with hematoxylin and eosin (H&E) 2 weeks after axotomy, from which muscle cells were harvested and protein extracted for evaluation.
Results:
Mitogen-activated protein kinases (MAPKs) were significantly activated by H2O2 treatment in C2C12 cells, which was ameliorated by NAC pretreatment. Furthermore, H2O2 induced apoptosis and death of C2C12 cells, which was prevented by NAC pretreatment. The weight of the gastrocnemius muscle was reduced in the axotomy group, which was prevented by NAC administration. Lastly, although muscle specimens from the axotomy group showed greater reductions in muscle fiber, the oral administration of NAC significantly inhibited amyotrophy via antioxidant effects.
Conclusion:
The current in vitro and in vivo study demonstrated the possible involvement of oxidative stress in sarcopenic pathology. NAC represents a potential anti-sarcopenic drug candidate, preventing amyotrophy and fatty degeneration.
Level Of Evidence:
4.
Insights
Oxidative stress contributes to sarcopenia, a muscle-wasting condition. N-acetyl-L-cysteine (NAC) demonstrated antioxidant effects, preventing muscle degeneration in cell and animal models of sarcopenia.
Area of Science:
- Muscle physiology and pathology
- Oxidative stress mechanisms
- Neurogenic muscle atrophy
Background:
- Oxidative stress is implicated in various pathologies, including musculoskeletal disorders.
- The precise role of oxidative stress in sarcopenia, a potential cause of lower back pain, remains unclear.
Purpose of the Study:
- To investigate the contribution of oxidative stress to muscle degeneration in sarcopenia.
- To evaluate the efficacy of antioxidant treatment using N-acetyl-L-cysteine (NAC) in a neurogenic sarcopenia animal model.
Main Methods:
- In vitro: C2C12 myoblasts treated with hydrogen peroxide (H2O2) and NAC; assessed apoptosis and viability.
- In vivo: Rodent model of neurogenic sarcopenia induced by sciatic nerve axotomy; NAC administered orally.
- Evaluated muscle weight, histological changes, and protein expression.
Main Results:
- H2O2-induced oxidative stress activated mitogen-activated protein kinases (MAPKs) in C2C12 cells, an effect reversed by NAC.
- NAC pretreatment prevented H2O2-induced apoptosis and cell death in vitro.
- NAC administration mitigated gastrocnemius muscle weight loss and fiber reduction in the axotomy model, demonstrating antioxidant effects against amyotrophy.
Conclusions:
- Oxidative stress plays a role in sarcopenic pathology, as evidenced by in vitro and in vivo findings.
- N-acetyl-L-cysteine (NAC) shows potential as an anti-sarcopenic therapeutic agent, effectively preventing muscle atrophy and fatty degeneration.
Related Concept Videos
01:31Skeletal Muscle Relaxants: Therapeutic Uses
01:48Classification of Skeletal Muscle Fibers
Slow-Twitch Muscle Fibers
Slow oxidative, muscle fibers appear red due to large numbers of capillaries and high levels of...
01:15Overview of Skeletal Muscle
01:29Relaxation of Skeletal Muscles
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open....
01:28Disorders of the Skeletal Muscle
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
01:19Naming Skeletal Muscles
The key factors used in naming muscles include: