Influence of simvastatin on myocardial antioxidant protection in rats with hypercholesterolemia
Background. Various experimental and clinical data on the mechanisms of statin-induced myopathy are available in the literature. At the same time, information about changes of antioxidant system in target organs following statin intake is very contradictory. Considering intracellular antioxidant status underlying defense reactions, it is advisable to analyze the main links of myocardial antioxidant protection in experimental model of statin-induced myopathy. Objective. To study myocardial antioxidant protection in experimental model of simvastatin-induced myopathy. Material and methods. The study was carried out on outbred male rats at the Rostov State Medical University (the Department of General and Clinical Biochemistry No. 1). Animals were divided into 3 groups. The control group (35 rats) enrolled intact animals; the comparison group (35 rats) included intact animals undergoing 2-month simvastatin therapy. There were also 2 experimental groups by 35 rats: group 1 - animals with induced hypercholesterolemia, group 2 - animals with induced hypercholesterolemia undergoing 2-month simvastatin therapy. We analyzed myocardial enzymes of antioxidant protection: superoxide dismutase (SOD), catalase, glutathione reductase, glutathione peroxidase (GPO) and concentration of reduced glutathione (GSH). Statistica 10.0 and Excel Microsoft programs were used for statistical analysis. Results. Introduction of an aggressive dose of simvastatin to animals with a physiological course of metabolic processes, as well as under conditions of experimental hypercholesterolemia causes a progressive disruption of the main mechanisms of myocardial antioxidant protection. This process is expressed by reduced activity of SOD, GPO and GSH concentration. Conclusion. In case of statin-induced myopathy, myocardium along with skeletal muscles can be the target organ for adverse side effects of statins. Our experimental data can be used as a theoretical basis for development of schemes for metabolic correction of biochemical abnormalities in the myocardium following high-dose statin therapy.