In a rat model, Mito-TEMPO treatment shows potential to reduce muscle atrophy during functional unloading, suggesting therapeutic avenues for atrophy prevention.
Functional unloading of skeletal muscles is observed during spaceflight, prolonged bed rest, or limb immobilization. In this case, skeletal muscle atrophy develops, which is a serious consequence for health and a noticeable decrease in quality of life. In addition, during functional unloading, mitochondrial dysfunction is observed and the release of reactive oxygen species (ROS) by mitochondria increases. It is known that some antioxidants can reduce the manifestation of atrophy during functional unloading. We hypothesized that the mitochondrial-specific antioxidant Mito-TEMPO would block the accumulation of mitochondrial ROS, which would lead to the prevention of an increase in ubiquitin ligase mRNA expression and prevent a decrease in anabolic parameters during 7-day functional unloading, which together could inhibit atrophy development. To test the hypothesis, we used a 7-day rat hindlimb suspension model of functional unloading. In our study, animals treated with Mito-TEMPO during 7-day suspension partially prevented the decrease in soleus muscle fiber cross-sectional area, the increase in the expression of in and mRNA expression, and the decrease in the content of rRNA. In addition, Mito-TEMPO reduced ROS-dependent oxidation of tropomyosin during 7-day suspension in the rat soleus muscle. Thus, the accumulation of mitochondrial ROS in the soleus muscle during 7-day functional unloading affects both protein synthesis and degradation, which is reflected in a decrease in muscle fiber cross-sectional area in the rat soleus muscle.
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D. A. Sidorenko (2025) studied this question.
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