Некоторые особенности изменения углеводно-энергетического обмена в миокарде и скелетных мышцах крыс под влиянием симвастатина

E. S. Belousova; Z. I.  Mikashinovich; E. V.  Vinogradova; T.D.  Loseva

doi:10.34687/2219-8202.JAD.2024.01.0003

Authors

E. S. Belousova Rostov State Medical University
Z. I. Mikashinovich Rostov State Medical University
E. V. Vinogradova Rostov State Medical University
T.D. Loseva Rostov State Medical University

DOI:

https://doi.org/10.34687/2219-8202.JAD.2024.01.0003

Keywords:

statins, statin myopathy, mitochondrial dysfunction, energy metabolism.

Abstract

The purpose of the study was a comprehensive analysis of biochemical changes in the skeletal muscles and myocardium of rats after the administration of Simvastatin.
Materials and methods. The study was conducted on outbred male rats (4 groups of 35 individuals) aged 12-14 months (300-350 g). The control group (intact animals) received the general diet of the vivarium and 2 ml of purified water daily through an esophageal tube. Animals of group 1 were also on a standard vivarium diet, plus they received an aqueous suspension of simvastatin through an esophageal tube at a dose of 0.012 g/kg body weight once daily for 2 months. In rats of groups 2 and 3, hypercholesterolemia was induced for 3 months, after diagnosis of which, animals
of group 2 were on a diet without the addition of simvastatin for two months, and animals of group 3 were administered simvastatin at a dose of 0.012 g/kg body weight once a day during the same period in the form of an aqueous suspension through an esophageal tube. In the myocardium
and skeletal muscles of animals, the activity of dehydrogenases of the Krebs cycle, cytochrome oxidase, the content of pyruvic acid and lactate were determined.
Results. The mechanisms of emergency restructuring of myocardial and skeletal muscle metabolism under the action of Simvastatin depended on the initial functional state of the organism.
In animals of group 1, under the influence of Simvastatin, an emergency metabolic
rearrangement was detected, aimed at activating glycolysis and oxidation of NAD-dependent substrates, as indicated by an increase in lactate levels and pyruvate dehydrogenase activity. The dynamics of the level of lactate and pyruvate and the activity of energy metabolism enzymes in the conditions of modeling alimentary hypercholesterolemia after the administration of Simvastatin reflects a tendency to reduce the severity of hypoxic changes caused by HC, but at the same time, indicates the inferiority of protective intracellular mechanisms and the formation of mitochondrial dysfunction.
Conclusion. Analysis of the revealed changes showed that the myocardium, as a special type of muscle tissue, can be subjected to damaging effects during long-term use of Statins.

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Author Biographies

E. S. Belousova, Rostov State Medical University

Candidate of Biological Sciences, Associate Professor, Head of the Department of Pharmaceutical Chemistry and Pharmacognosy

Z. I. Mikashinovich, Rostov State Medical University

Doctor of Biological Sciences, Professor, Professor of the Department of General and Clinical Biochemistry № 1

E. V. Vinogradova, Rostov State Medical University

Candidate of Medical Sciences, Associate Professor of the Department of Pharmaceutical Chemistry and Pharmacognosy

T.D. Loseva, Rostov State Medical University

Candidate of Medical Sciences, Associate Professor of the Department of Chemistry of the Preparatory Faculty for the Education of Foreign Citizens

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