The role of dihydroquercetin in the molecular mechanisms of myocardial protection in dust- induced pathology

Abstract

Introduction. Dust-induced lung pathology in miners is often combined with cardiovascular diseases such as coronary heart disease, hypertension, and atherosclerosis. In this regard, the search for ways to prevent the development of combined pathology with dust effects on the body is an urgent problem in occupational health.The aim of the study was to explore the effect of a complex preparation with dihydroquercetin on the level of protective proteins and myocardial morphostructure in the dynamics of dust-induced pathology development when inhaling coal-rock dust.Materials and methods. The study was conducted on white laboratory male rats weighing 200–250 g. The animals were divided into two groups: rats that inhaled coal-rock dust in the priming dust chamber daily for 4 hours for 1, 3, 6, 9 and 12 weeks; rats that received a daily complex drug with dihydroquercetin. The concentration of IL–6 proinflammatory cytokine and cardiomarkers (B-type brain natriuretic peptide, vascular endothelial growth factor, and fractalkin) was determined in the blood by enzyme immunoassay. In the cytosolic fraction of heart tissue, the level of expression of the hypoxia-induced transcription factor HIF — 1α, the inducible forms of proteins HSP72 and heme-oxygenase–1 was determined.Results. Prolonged dust exposure in the early stages (1–3 weeks) increased the expression of HIF–1α transcription factor and stress-inducible proteins — HSP72 and HOx–1 — in the myocardium. An increase in the dust exposure period of more than 6 weeks was accompanied by a decrease in the level of the HIF–1α transcription factor to control values, but the intensive synthesis of HSP72 and HOx–1 was maintained. In addition, the dynamics of long-term dust exposure to the body changed the level of cardiomarkers in the blood serum: 1) increased vascular endothelial factor; 2) fractalkin and IL–6 decreased in the early stages, as well as brain natriuretic peptide type B — the entire period of the study. By week 12 of dust exposure in the myocardial tissue it was revealed: dystrophic changes of a protein nature, signs of apoptosis, atrophy of some fibers and the development of diff use cardiosclerosis. Daily administration of a complex drug with dihydroquercetin to laboratory animals with prolonged exposure to coal-rock dust for 12 weeks led to the restoration of the level of protective cardiomarkers to control values and reduced the severity of morphological changes in the heart tissue.Conclusions. The administration of a complex drug with dihydroquercetin during prolonged dust exposure on the body has a cardioprotective effect, which is confirmed by the achievement of control levels of cell proliferation factors (B- type brain natriuretic peptide), angiogenesis (vascular endothelial factor), proinflammatory (IL–6) and anti-inflammatory response (CX3CL1), as well as a decrease in the severity of dystrophic changes in myocardial muscle fibers and almost complete disappearance of lymphocytic infiltration in heart vessels.Th e authors declare no confl ict of interests.