Abstract
Background. Statin therapy may be accompanied by a toxic effect on skeletal muscle and liver cells, the molecular mechanisms of which have not yet been fully understood.Aim.To clarify the peculiarities of changes in the oxygen transport function of erythrocytes and antioxidant mechanisms in erythrocytes and muscles of animals with prolonged administration of statins (simvastatin).Materials and methods.The study was conducted on outbred male rats, which during the experiment were randomly assigned to following groups: the control group contained animals on a common ration of the vivarium, the group of comparison – animals with induced hypercholesterolemia, the main group – animals with induced hypercholesterolemia treated with simvastatin. In erythrocytes and muscle tissue of animals, indicators characterizing the state of antioxidant defense and carbohydrate metabolism were determined.The results.The experiment showed that the administration of simvastatin to animals was characterized by aggravation of hypoxia due to hypercholesterolemia, as indicated by a sharp increase in the concentration of 2,3-BPG and lactate in erythrocytes of animals, as well as a significant decrease in the activity of G6PD. In the muscle tissue of animals, there was a decrease in the concentration of pyruvic acid and lactate relative to the comparison group, which indicates their intensive participation in metabolic processes.Conclusion.Based on the data obtained, it can be assumed that the peculiarity of the action of statins in erythrocytes is the increased oxygen delivery to the tissues, which in muscles was accompanied by a decrease in the level of oxidized products. At the same time, against the background of the use of statins, despite the positive direction of adaptive reactions, signs of oxidative stress remain, which is documented by the imbalance of the SOD-catalase system and a decrease in the activity of glutathione-dependent reactions
Highlights
Statin therapy may be accompanied by a toxic effect on skeletal muscle and liver cells, the molecular mechanisms of which have not yet been fully understood
Активность ферментов антиоксидантной защиты в мышцах животных исследуемых групп The activity of enzymes of antioxidant protection in the muscles of animals in the studied groups
Обращают на себя внимание значительные изменения активности глутатионзависимых ферментов: дальнейшее резкое снижение активности ГПО на 63,13 % (p1 < 0,001), ГР на 37,5 % (p1 < 0,001) и концентрации GSH на 49,83 % (p1 < 0,001) относительно показателей группы сравнения, что указывает на снижение адаптивного потенциала глутатионовой системы миоцитов
Summary
Statin therapy may be accompanied by a toxic effect on skeletal muscle and liver cells, the molecular mechanisms of which have not yet been fully understood. В эритроцитах животных этой группы было отмечено увеличение концентрации лактата на 42,77 % (p < 0,001) по сравнению с контрольной группой, в то время как концентрация ПВК снизилась на 15,84 % (p < 0,05) Параллельно в мышечной ткани животных группы сравнения на фоне гиперхолестеринемии было выявлено резкое увеличение концентрации лактата на 73,23 % (p < 0,001), ПВК на 247,11 % (p < 0,001) относительно контрольной группы
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