Эффективность α-липоевой кислоты в компенсации расстройств сократительной функции скелетной мышцы, вызванных длительным введением дексаметазона, в модельных экспериментах на животных

Abstract

The aim of the study was to evaluate the efficacy of a-lipoic acid (a-LA) in correcting disorders of the contractile function of a mixed type skeletal muscle (m. tibial anterior) induced by chronic dexamethasone (DM) treatment in an animal model.Methods. Experiments were performed on sexually mature female rats (190-200 g) divided into four groups: control (intact rats, C group, n=10), experimental group 1 (30-day dexamethasone treatment, DM group, n=10), experimental group 2 (30-day dexamethasone plus a-lipoic acid treatment, DM+a-LA group, n=10), and experimental group 3 (30-day a-lipoic acid treatment, a-LA group, n=10). Dexamethasone (KRKA, Slovenia) was administered every two days, i.p., at a dose of 0.25 mg/kg, which was equivalent to the clinical therapeutic dose. a-Lipoic acid (Berlition-600, BERLIN-CHEMIE, Germany) was administered daily at a dose of 35 mg/kg, s.c. Stimulation electromyography and myography were performed in an acute experiment, under sodium thiopental (100 mg/kg) anesthesia, on day 30. Electrophysiological and contractile parameters of the anterior tibial muscle were recorded during stimulation with suprathreshold electrical current via the fibular nerve.Results. a-LA in combination with DM prevented decreases in the number of activated muscular motor units (MMU) and muscle mass, the degree of the muscle post-tetanic potentiation, and disorders of contractile and temporal parameters of single and tetanic contractions, which were typical for animals of the DM group. The a-LA plus DM treatment even significantly increased the relaxation rate of a single contraction (by 34%) and the rate of tetanic contraction development (by 80%) compared to the control group (p<0.05), which were also typical for the a-LA group. These facts indirectly evidence the absence of pronounced dystrophic changes in muscle fibers in animals of the DM+a-LA group. At the same time, although the shortened period of maximum muscle work capacity, which was typical for the DM group, was not observed in the DM+a-LA group, this period was no longer than in the control either, as distinct from the a-LA group. This fact suggests the absence of positive effects of a-LA on the muscle work capacity when a-LA is administered in combination with DM. The a-LA+DM treatment reversed the increased fatigue and the reduced ability to recover of the muscle after fatigable work (FW) observed in the DM group. Moreover, the a-LA+DM treatment even increased the rate of muscle recovery after FW, which was also characteristic for the a-LA group. This was confirmed by the absence of decreased rates of muscle shortening after FW, which was typical for the DM group, and by the absence of significant decreases in the single contraction amplitude and the number of activated MMU after FW, which was typical not only for the DM group, but also for the control.Conclusion. The changes in muscle functional parameters in the DM and DM+a-LA groups evidence pronounced contractile disorders and impaired ability of the muscle to recover after FW in the DM group. In the DM+a-LA group, the muscle contractile function was not significantly impaired. Moreover, the muscle ability to recover after FW was not reduced in the DM+a-LA-group. In this group, the ability to recover was even increased compared to the control, which was also characteristic for the a-LA-group. These facts allow considering a-LA as a possible therapy for correction of steroid myopathy.