Biochemical changes in rat muscle tissue with prolonged use of simvastatin

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.