EFFICIENCY OF ALPHACALCIDOL IN COMPENSATION OF DISORDERS OF CONTRACTILE FUNCTIONS OF THE SKELETAL MUSCLE WITH DEXAMETHAZONE HYPERCORTICISM IN EXPERIMENTS ON RATS
The aim of the research was to study in experiments on rats the effectiveness of alfacalcidol (ALF, 0,06 μg/kg/day) in compensating of disorders of the contractile function of skeletal muscle induced by prolonged administration of dexamethasone (DM, 0,25 mg/kg/2 days, treated for 30 days). Methods. The experiments were performed on sexually mature female rats (195-205 g), divided into 4 groups: control (n=10, C-group), first experimental (n=10, treated dexamethasone, DM-group), second experimental (n=10, treated dexamethasone in combination with alfacalcidol, DM+ALF-group) and third experimental (n=10, treated alfacalcidol, ALF-group). The medicines were administered in doses adequate to the therapeutic for humans for 30 days: dexamethasone (KRKA, Slovenia) - once every 2 days, i.p., at a dose of 0,25 mg/kg, alfacalcidol (trademark “Alpha D3-Teva", Catalent Germany Eberbach GmbH, Germany) - daily, orally, at a dose of 0,06 μg/kg. On anesthetized animals (sodium thiopental, 100 mg/kg) some functional parameters of the tibialis anterior muscle were studied using the myography method. Results. ALF, administered in combination with DM, prevented a decrease in muscle mass, which was typical for the DM-group, but a decreasing tendency of muscle mass in the DM+ALF-group still persisted. The administration of ALF in combination with DM prevented a typical for DM-group decrease in amplitude and weakened the degree of lengthening of the latent period and a decrease in the rate of shortening and relaxation of single contractions, and also significantly reduced the decrease of the degree of post-tetanic potentiation in comparison with the DM-group. These facts indirectly indicate in a favor of a less pronounced of dystrophic changes in fast muscle fibers in the muscle of animals of the DM+ALF-group in comparison with the DM-group. ALF, administered in combination with DM, prevented deterioration in the amplitude and in the rate of tetanic contraction during muscle work with a greater load (70 g), which was typical for the DM-group. Moreover, at a low external load (20 g) an increase in the rate of development of tetanus (by 47 %) was observed in animals of the DM+ALF-group in comparison with the control (p<0,05), what was typical for the ALF-group. At the same time, in the DM+ALF-group a more pronounced decrease in the percentage of tetanus rate under a load of 70 g relative to that under a load of 20 g were retained, which was typical for the DM-group and indirectly indicated in a favor of some deterioration in the strength characteristics of the muscle. ALF, administered in combination with DM, prevented the shortening of the period of maximum muscle working capacity, which was typical for the DM-group. In addition, the muscle of animals of the DM+ALF-group was characterized by a higher rate of recovery after fatigable work (FW) in comparison with the DM-group. This is evidenced by the absence of a decrease in the amplitude of single muscle contractions in animals of the DM+ALF-group after FW, which is typical for the DM-group and control, as well as the absence of a decrease in the rate of shortening and relaxation during a single contraction after FW, which is characteristic for the DM-group. Conclusion. The changes in the functional parameters of the muscle of animals of the DM- and DM+ALF-groups indicate in a favor of pronounced contractile disorders in individuals of the DM-group, as well as a reduced ability of its muscles to recover after FW. ALF, administered in combination with DM, significantly weakened the severity of contractile disorders and prevented the deterioration of muscle resistance to fatigue, which was typical for the DM-group. At the same time, ALF could not completely prevent a decrease in muscle mass, as well as a deterioration of some rate parameters of a single muscle contraction and its strength characteristics.