Some features of musclemetabolic processes changes with prolonged use of simvastatin and thioctic acid in the experiment

Abstract

Aim. To identify biochemical changes in the muscle tissue of rats in long-term comprehensive administration of simvastatin and thioctic acid (lipoic acid). Methods. The study was conducted on 120 male outbred rats. The animals were divided into 2 groups: group 1 - intact animals fed common vivarium diet, group 2 - with induced essential hypercholesterolemia. The animals of the experimental group were divided into three subgroups: subgroup 1 - animals that received a diet without the additional drugs; subgroup 2 - those who received simvastatin, and subgroup 3 - those who received simvastatin in combination with thioctic (lipoic) acid. At the end of experiment the concentrations of pyruvic acid, lactate, and reduced glutathione, activity of glutathione reductase, glutathione peroxidase, succinate dehydrogenase and cytochrome oxidase were determined in the muscle of experimental animals. Results. The development of hypercholesterolemia was found to be characterized by the accumulation of pyruvic acid and lactate in the muscles of rats, which may indicate metabolic acidosis formation. The activity of antioxidant enzymes was multidirectional, indicating disorganization of the main mechanisms of antioxidant defense. The dynamics of antioxidant enzymes activity in animal muscles after the administration of simvastatin indicates aggravation of antioxidant defense disorders. The decrease of the concentration of pyruvic acid and lactate indicates a decrease of the severity of hypoxia. At the same time, decrease of the activity of cytochrome oxidase and succinate dehydrogenase indicates the prevalence of anaerobic bioenergetic mechanisms. After administration of simvastatin in combination with thioctic (lipoic) acid, a decrease of the level of pyruvic acid and lactate to the levels in the control group, an increase of the activity of succinate dehydrogenase and cytochrome oxidase, and increase of the reduced activity of glutathione peroxidase and the concentration of reduced glutathione were detected. Conclusion. Analyzing the data obtained, thioctic (lipoic) acid with the concomitant use of a statin can be assumed to provide reduction of the severity of hypoxia, stabilization of the bioenergetic and antioxidant processes that can be used for targeted impact on certain pathobiochemical violations in muscle tissue with chronic administration of statins.