Biochemical changes in rat muscle tissue with prolonged use of simvastatin
- Authors: Vinogradova EV1
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Affiliations:
- Rostov State Medical University
- Issue: Vol 99, No 2 (2018)
- Pages: 240-244
- Section: Experimental medicine
- URL: https://journal-vniispk.ru/kazanmedj/article/view/8413
- DOI: https://doi.org/10.17816/KMJ2018-240
- ID: 8413
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Abstract
Aim. Analysis of biochemical changes in rat muscle tissue after prolonged use of simvastatin.
Methods. The study was conducted on mongrel male rats. Three groups were identified: control group (intact animals), comparison group (animals with induced hypercholesterolemia not reeciving the drugs), and experimental group (animals with induced hypercholesterolemia receiving simvastatin 0.0012 g/100 g of weight once a day for 2 months as an aqueous suspension through the esophageal probe). Metabolite concentration of glycolysis (pyruvic acid and lactate), activity of antioxidant protection enzymes (reduced glutathione, superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase), titin isoforms and proteolytic fragments of titin and nebulin concentration were determined in the muscles of animals.
Results. After administration of simvastatin to animals with induced hypercholesterolemia, a decrease in the concentration of glycolysis metabolites (pyruvic acid and lactate) compared to comparison group was revealed, as well as multidirectional changes in the activity of antioxidant protection enzymes (decrease in activity of superoxide dismutase, glutathione peroxidase, and glutathione reductase, decreased concentration of reduced glutathione, but catalase activity remained unchanged). The analysis of structural changes in animal muscle tissue after administration of simvastatin revealed a decrease in the concentration of NT- and N2A-titin isoforms and practically complete absence of nebulin compared to the animals from the comparison group. At the same time an increase in the concentration of proteolytic fragments of titin (T2) by 1.3 times was recorded.
Conclusion. The study showed that the basis of myotoxicity of statins in their long-term use is disintegration of enzyme antioxidant processes, as well as tissue hypoxia, leading to destruction of muscle fibers and prevalence of proteolytic processes.
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##article.viewOnOriginalSite##About the authors
E V Vinogradova
Rostov State Medical University
Author for correspondence.
Email: mod8792@mail.ru
Rostov-on-Don, Russia
References
- Mikashinovich Z.I., Belousova E.S., Vinogradova E.V., Semenets I.A. Еnzymatic antioxidant protection in muscles of rats under long-term administration of simvastatin. Meditsinskiy vestnik Bashkortostana. 2017; 12 (1): 54–57. (In Russ.)
- Mikashinovich Z.I., Belousova E.S. Impairment of energy-dependant processes in the muscle tissue as a pathogenetic mechanisms of statin-induced myopathy. Byulleten' eksperimental'noy biologii i meditsiny. 2016; 162 (10): 426–430. (In Russ.)
- Kalinina E.V., Chernov N.N., Aleid R. et al. Current views of antioxidative activity of glutathione and glutathione-depending enzymes. Vestnik RAMN. 2010; 3: 46–54. (In Russ.)
- Mikashinovich Z.I., Letunovskiy A.V., Volzhin O.O., Belousova E.S. Biokhimicheskie issledovaniya slyuny v klinicheskoy praktike. (Biochemical studies of saliva in clinical practice.) Rostov-na-Donu: Izdatel'stvo RostGMU. 2004; 80 p. (In Russ.)
- Vikhlyantsev I.M., Podlubnaya Z.A. Titin isoform composition in the muscles in pathological processes. Biofizika. 2008; 53 (6): 1058–1065. (In Russ.)
- Vikhlyantsev I.M., Podlubnaya Z.A. New titin (connectin) isoforms and their functional role in striated muscles of mammals: facts and suppositions. Uspekhi biologicheskoy khimii. 2012; 52: 239–280. (In Russ.)
- Dubinina E.E. The role of reactive oxygen species as signal molecules in tissue metabolism under conditions of oxidative stress. Voprosy meditsinskoy khimii. 2001; 47 (6): 561–581. (In Russ.)
- Lakomkin V.L., Kapel'ko V.I., Lankin V.Z. et al. Effect of β-hydroxy-β-methylglutaryl coenzyme a reductase inhibitor atorvastatin on contractility of the isolated rat heart under normal conditions and during oxidative stress. Byulleten' eksperimental'noy biologii i meditsiny. 2007; 143 (4): 383–385. (In Russ.)
- Kulinskiy V.I., Kolesnichenko L.S. System of glutathione I. Synthesis, transport, glutathione transferases, glutathione peroxidases. Biomeditsinskaya khimiya. 2009; 55 (3): 255–277. (In Russ.)
- Mikashinovich Z.I., Belousova E.S. Biochemical changes in erythrocytes as a molecular marker of cell damage during long-term simvastatin treatment. Kletochnye tekhnologii v biologii i meditsine. 2016; 2: 122–126. (In Russ.)
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