OPTIMIZATION OF SKELETAL MUSCLE ENERGY SUPPLY UNDER GRADED PHYSICAL EXERCISE THROUGH SUCCINATE-DEPENDENT METABOLIC CORRECTION
DOI:
https://doi.org/10.17721/1728.2748.2026.104.19-24Keywords:
physical exertion, energy metabolism, metabolism, skeletal muscle, succinateAbstract
Background. Graded physical exertion (GPE) is accompanied by increased muscular energy demand, which may induce adaptive changes in the mitochondrial apparatus and microcirculatory system. Under conditions of hypoxic stress, alterations such as cristae disorganization, mitochondrial swelling, and disturbances in redox homeostasis may occur. Succinate, a substrate of the respiratory chain, is considered not only an intermediate of the tricarboxylic acid cycle but also a potential modulator of redox balance and mitochondrial biogenesis. The aim of this study was to evaluate the possible effects of succinate-dependent metabolic modulation using 2-ethyl-6-methyl-3-hydroxypyridine succinate on mitochondrial morphometric parameters and histohematogenous barrier thickness in the gastrocnemius muscle of trained and untrained rats during muscle activity.
Methods. The experiment was conducted in male rats allocated into the following groups: control; untrained with GPE; untrained with GPE receiving 2-ethyl-6-methyl-3-hydroxypyridine succinate; trained with GPE; and trained with GPE receiving 2-ethyl-6-methyl-3-hydroxypyridine succinate. Transmission electron microscopy with morphometric analysis was used to evaluate subsarcolemmal and intermyofibrillar mitochondrial subpopulations. The number of mitochondria (units/μm²), the proportion of structurally altered organelles (%), mitochondrial diameter (μm), and histohematogenous barrier thickness (nm) were assessed. Statistical analysis was performed using STATISTICA 6.0. Data are presented as mean ± SEM; normality was verified with the Shapiro–Wilk test, intergroup differences were analyzed by one-way ANOVA, and p<0.05 was considered statistically significant.
Results. In untrained animals, GPE was associated with a reduction in mitochondrial density, an increase in the proportion of structurally altered mitochondria, and enlargement of mitochondrial diameter. Histohematogenous barrier thickness was also significantly increased. Administration of 2-ethyl-6-methyl-3-hydroxypyridine succinate was accompanied by an increase in mitochondrial density, a decrease in the proportion of damaged organelles, partial normalization of mitochondrial diameter, and reduced barrier thickness. In trained animals, a higher baseline mitochondrial reserve was observed; however, GPE was associated with an increased proportion of structurally altered mitochondria. In the presence of 2-ethyl-6-methyl-3-hydroxypyridine succinate, a further increase in mitochondrial density, a reduction in altered organelles, and decreased barrier thickness were noted.
Conclusions. Succinate-dependent metabolic modulation may contribute to optimization of mitochondrial and microcirculatory parameters in skeletal muscle during graded physical exertion. In untrained animals, the observed effects appear to be predominantly compensatory, whereas in trained animals they may be interpreted as protective and stabilizing. The findings suggest a coordinated influence on the "microcirculation–mitochondria" functional axis, potentially creating structural conditions favorable for more efficient aerobic energy metabolism.
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