Comparative analysis of metabolic and structural changes in the skeletal muscles and myocardium of rats on the background of long-term administration of simvastatin

Abstract

Objective: to conduct a comparative analysis of the dynamics of changes in the end products of glycolysis and the isoform composition of the giant protein - titin and nebulin in the skeletal and cardiac muscles of animals with HC during long-term administration of simvastatin. Materials and methods: the study was conducted on rats that were kept on a high-fat and high-carbohydrate  diet for three months. After GC confirmation, the animals were divided into groups: group 1 received only the experimental diet; group 2 received simvastatin in the form of an aqueous suspension for two months at the rate of 0.012 g/kg of animal weight once a day. The control group of animals was kept on the general diet of the vivarium. Results: The formation of HCh was accompanied  by the accumulation  of pyruvate and lactic acid both in the myocardium and in muscle tissue. The revealed metabolic changes reflect structural disorders and indicate the formation of hypoxia. Against the background of the introduction of simvastatin, both in the myocardium and in the skeletal muscles, a decrease in the level of pyruvate and lactic acid was noted and these indicators approached the values of the control group. Such changes reflect a tendency to restore the integration of intracellular metabolic processes. However, in the study of titin and nebulin proteins against the background of the use of simvastatin, both in the myocardium and in skeletal muscles, structural changes were noted: accumulation  of the proteolytic T-fragment, a decrease in the content of intact titin isoforms. Also, statin-induced structural abnormalities have been identified in earlier studies of rat muscle biopsies. Conclusion: The conducted comparative study clearly demonstrates that the myocardium, along with skeletal muscles, is the target organ of the toxic effect of statins. Based on this, the data obtained as a result of the study, it is important to take into account the pharmacotherapy with statins.