The Protective Effects of γ-Tocotrienol on Muscle Stem Cells Through Inhibiting Reactive Oxidative Stress Production

Shuo Yang; Juan Yang; Huiwen Zhao; Rong Deng; Hancheng Fan; Jinfu Zhang; Zihao Yang; Huihong Zeng; Bohai Kuang; Lijian Shao

doi:10.3389/fcell.2022.820520

The Protective Effects of γ-Tocotrienol on Muscle Stem Cells Through Inhibiting Reactive Oxidative Stress Production

Front Cell Dev Biol. 2022 Mar 15:10:820520. doi: 10.3389/fcell.2022.820520. eCollection 2022.

Authors

Shuo Yang^{1

2}, Juan Yang^{1

2}, Huiwen Zhao³, Rong Deng^{1

2}, Hancheng Fan⁴, Jinfu Zhang^{1

2}, Zihao Yang^{1

2}, Huihong Zeng^{4

5}, Bohai Kuang³, Lijian Shao^{1

2

5}

Affiliations

¹ Department of Occupational Health and Toxicology, School of Public Health, Nanchang University, Nanchang, China.
² Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China.
³ Department of Biological Genetics, School of Basic Medicine, Nanchang University, Nanchang, China.
⁴ Department of Histology and Embryology, School of Basic Medicine, Nanchang University, Nanchang, China.
⁵ Jiangxi Provincial Key Laboratory of Interdisciplinary Science, Nanchang University, Nanchang, China.

Abstract

Pseudotrophic muscular dystrophy is a common clinical skeletal muscle necrotic disease, among which Duchenne muscular dystrophy (DMD) is the predominant. For such diseases, there is no clinically effective treatment, which is only symptomatic or palliative treatment. Oxidative stress and chronic inflammation are common pathological features of DMD. In recent years, it has been found that the pathophysiological changes of skeletal muscle in DMD mice are related to muscle stem cell failure. In the present study, we established a DMD mice model and provided tocotrienol (γ-tocotrienol, GT3), an antioxidant compound, to explore the relationship between the physiological state of muscle stem cells and oxidative stress. The results showed that the application of GT3 can reduce ROS production and cellular proliferation in the muscle stem cells of DMD mice, which is beneficial to promote the recovery of muscle stem cell function in DMD mice. GT3 treatment improved the differentiation ability of muscle stem cells in DMD mice with increasing numbers of MyoD⁺ cells. GT3 application significantly decreased percentages of CD45⁺ cells and PDGFRα⁺ fibro-adipogenic progenitors in the tibialis anterior of DMD mice, indicating that the increased inflammation and fibro-adipogenic progenitors were attenuated in GT3-treated DMD mice. These data suggest that increased ROS production causes dysfunctional muscle stem cell in DMD mice, which might provide a new avenue to treat DMD patients in the clinic.

Keywords: Duchenne muscular dystrophy; cellular proliferation; muscle stem cells; oxidative stress; γ-tocotrienol.