Abstract
The mdx mouse phenotype aggravated by chronic exercise on a treadmill makes this murine model more reliable for the study of muscular dystrophy. Thus, to better assess the Tempol effect on dystrophic pathways, the analyses in this study were performed in the blood samples and diaphragm muscle from treadmill trained adult (7–11-weeks old) mdx animals. The mdx mice were divided into three groups: mdxSed, sedentary controls (n = 28); mdxEx, exercise-trained animals (n = 28); and mdxEx+T, exercise-trained animals with the Tempol treatment (n = 28). The results demonstrated that the Tempol treatment promoted muscle strength gain, prevented muscle damage, reduced the inflammatory process, oxidative stress, and angiogenesis regulator, and up regulated the activators of mitochondrial biogenesis. The main new findings of this study are that Tempol reduced the NF-κB and increased the PGC1-α and PPARδ levels in the exercise-trained-mdx mice, which are probably related to the ability of this antioxidant to scavenge excessive ROS. These results reinforce the use of Tempol as a potential therapeutic strategy in DMD.
Highlights
Duchenne muscular dystrophy (DMD) represents one of the most devastating types of muscular dystrophies, which affects one in 3,000–6,000 male children (Choi et al, 2016)
We demonstrated that Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a synthetic antioxidant that mimics the role of superoxide dismutase (SOD), improved the dystrophic phenotype (Hermes et al, 2019) and contributed to the normalization of the redox homeostasis (Hermes et al, 2020) in young mdx mice during the acute dystrophic disease phase
In agreement with previous studies (Camerino et al, 2014; for review Hyzewicz et al, 2015), the present study found that exercise training substantially affects the dystrophic features of adult mdx mice by making them more closely resemble DMD
Summary
Duchenne muscular dystrophy (DMD) represents one of the most devastating types of muscular dystrophies, which affects one in 3,000–6,000 male children (Choi et al, 2016). Previous work showed that DMD is a multifactorial disease, whereby inflammation, mitochondrial dysfunction, altered angiogenesis, and oxidative stress are among the main promoters of the dystrophic features (Guiraud and Davies, 2017). Our research group has evaluated the effects of some antioxidant drugs on the dystrophic muscle of mdx mice, which was the experimental DMD model We demonstrated that Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a synthetic antioxidant that mimics the role of superoxide dismutase (SOD), improved the dystrophic phenotype (reducing myonecrosis and the inflammatory process) (Hermes et al, 2019) and contributed to the normalization of the redox homeostasis (Hermes et al, 2020) in young mdx mice during the acute dystrophic disease phase (about three weeks post-natal age). Burns et al (2017) reported that Tempol supplementation restores the diaphragm force and metabolic enzyme activities in adult mdx mice
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