Organ-specific expression of protective proteins under the conditions of dust exposure to the body (experimental study)

The objective of the study was to evaluate the organ-specific features of the expression of protective proteins of the HSP family in response to prolonged dust exposure in an experiment.Material and methods. The experiments were performed on 60 male Wistar rats weighing 200-250 g. The animals were divided into groups: rats inhaled coal-rock dust in the priming dust chamber for 4 hours daily for 6 weeks (average concentration 50 mg/m3), and the control rats (they were in an equal volume chamber, where the same temperature and air exchange conditions were maintained, but without the supply of coal-rock dust). In the cytoplasmic fraction of the lungs, heart, liver, and brain, the levels of HSP72 and heme oxygenase-1 (HOx-1) were determined by Western blot analysis.Results. The prolonged exposure of coal-rock dust to the body changed the level of intracellular proteins HSP72 and HOx-1 in the lungs, heart, liver, and brain. An increase in both HSP72 and HOx-1 levels occurred in the lungs and brain tissue; a significant increase in HOx-1 was recorded in the heart and HSP72 in the liver. These data indicate the organ-specific expression of intracellular proteins during dust exposure to the body. The following molecular mechanisms are involved in the development of the response to prolonged inhalation of coal-rock dust: 1) in the lungs and brain - both stress (HSP72) and hypoxic (HOx-1) components; 2) in the heart - a hypoxic component, manifested by the intensive synthesis of HOx-1 throughout the study period; 3) in the liver - a stress component due to significant expression of HSP72, which is associated with the manifestation of a protective effect for both the organ itself and the body as a whole.Conclusion. The results obtained indicate the organ-specificity of the cellular response of the body to the prolonged exposure to industrial dust. A change in the expression level of HSP72 and HOx-1 characterizes the degree of protection of organs from damage caused by inhalation of coal-rock dust, which grows in the series as liver < heart < lungs and brain.

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

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2020-60-3-178-183 ◽

2020 ◽

pp. 178-183

Author(s):

A. G. Zhukova ◽

A. S. Kazitskaya ◽

N. N. Zhdanova ◽

L. G. Gorokhova ◽

N. N. Mikhailova ◽

...

Keyword(s):

Transcription Factor ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Heart Tissue ◽

The Body ◽

Dust Exposure ◽

Vascular Endothelial ◽

Coal Rock ◽

Complex Drug ◽

Rock Dust

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.

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Expression of protective proteins and morphological changes in the rat brain after prolonged exposure to dust

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2021-61-3-181-186 ◽

2021 ◽

Vol 61 (3) ◽

pp. 181-186

Author(s):

Anna G. Zhukova ◽

Maria S. Bugaeva ◽

Anastasiya S. Kazitskaya ◽

Oleg I. Bondarev ◽

Nadezhda N. Mikhailova

Keyword(s):

Free Radical ◽

Brain Tissue ◽

Morphological Changes ◽

The Body ◽

Dust Exposure ◽

Free Radical Processes ◽

Coal Rock ◽

Radical Processes ◽

Protective Proteins ◽

The Brain

Introduction. The fundamental mechanisms of the body's pathological reaction to coal and dust exposure are hypoxia, excessive activation of free radical processes, structural and metabolic disorders in various organs. Organ-specific molecular defense mechanisms begin to function in the form of changes in the level of proteins with antihypoxic (HIF-3a), chaperone (HSP72), and antioxidant functions (HOx-1 - heme-oxygenase, Prx-1 - peroxiredoxin) under damaging effects. Its high level contributes to the restoration of cells' functional state or indicates significant damage in tissues. Hypoxia and free radical processes are known to lead to severe brain damage and behavioral disorders. To date, little is known about the expression of protective proteins and morphological changes in the brain under prolonged exposure to coal-rock dust on the body. The study aimed to learn the level of intracellular protective proteins HIF-3a, HSP72, HOx-1, Prx-1, and morphological changes in the brain in the dynamics of long-term dust exposure. Materials and methods. Sixty white male Wistar rats weighing 200-250 g of the same age took part in the experiment. Dust exposure was modeled by way of dynamic inhalation priming of rats with coal-rock dust (coal of a gas-fat brand) in an intermittent mode for 12 weeks. We perform morphological studies of the brain after 1, 3, 6, 9, and 12 weeks of dust exposure. The cytosolic fraction of brain tissue researchers determined the expression level of HIF-3a, HSP72, HOx-1, and Prx-1 by Western blot analysis. We selected the activity of free radical processes in the brain tissue. Results. Long-term exposure to coal-rock dust on the body at the morphological level in the brain revealed changes that indicate the development of hypoxia and activation of free radical processes: microvascular disorders, pericellular edema, severe dystrophic damage to neurons, focal loss of neurons, activation of glial cells. Activation of the protective proteins HIF-3a, HSP72, HOx-1, and Prx-1 in the early stages (1-3 weeks) of coal-dust exposure provided compensation for free radical processes in brain neurons. An increase in the duration of dust exposure of more than six weeks influences a low level of HSP72, but high HIF-3a and Prx-1, indicating an increase in hypoxic and free radical damage brain. Conclusions. The results obtained to expand the understanding of the morphological and molecular mechanisms that occur in the brain tissue during prolonged dust exposure to the body are essential for developing methods for organ-specific pharmacological correction.

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Comparative assessment of morphological mechanisms of maintaining structural liver homeostasis in the dynamics of exposure to coal-rock dust and sodium fluoride on the body

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2020-60-3-189-194 ◽

2020 ◽

pp. 189-194

Author(s):

M. S. Bugaeva ◽

O. I. Bondarev ◽

N. N. Mikhailova ◽

L. G. Gorokhova

Keyword(s):

Sodium Fluoride ◽

Morphological Changes ◽

The Body ◽

System Level ◽

Production Factor ◽

Coal Rock ◽

The Impact ◽

Structural Homeostasis ◽

Rock Dust

Introduction. The impact on the body of such factors of the production environment as coal-rock dust and fluorine compounds leads to certain shift s in strict indicators of homeostasis at the system level. Maintaining the relative constancy of the internal environment of the body is provided by the functional consistency of all organs and systems, the leading of which is the liver. Organ repair plays a crucial role in restoring the structure of genetic material and maintaining normal cell viability. When this mechanism is damaged, the compensatory capabilities of the organ are disrupted, homeostasis is disrupted at the cellular and organizational levels, and the development of the main pathological processes is noted.The aim of the study is to compare the morphological mechanisms of maintaining structural homeostasis of the liver in the dynamics of the impact on the body of coal-rock dust and sodium fluoride.Materials and methods. Experimental studies were conducted on adult white male laboratory rats. Features of morphological mechanisms for maintaining structural homeostasis of the liver in the dynamics of exposure to coal-rock dust and sodium fluoride were studied on experimental models of pneumoconiosis and fluoride intoxication. For histological examination in experimental animals, liver sampling was performed after 1, 3, 6, 9, 12 weeks of the experiment.Results. The specificity of morphological changes in the liver depending on the harmful production factor was revealed. It is shown that chronic exposure to coal-rock dust and sodium fluoride is characterized by the development of similar morphological changes in the liver and its vessels from the predominance of the initial compensatory-adaptive to pronounced violations of the stromal and parenchymal components. Long-term inhalation of coal-rock dust at 1–3 weeks of seeding triggers adaptive mechanisms in the liver in the form of increased functional activity of cells, formation of double-core hepatocytes, activation of immunocompetent cells and endotheliocytes, ensuring the preservation of the parenchyma and the general morphostructure of the organ until the 12th week of the experiment. Exposure to sodium fluoride leads to early disruption of liver compensatory mechanisms and the development of dystrophic changes in the parenchyma with the formation of necrosis foci as early as the 6th week of the experiment.Conclusions. The study of mechanisms for compensating the liver structure in conditions of long-term exposure to coal-rock dust and sodium fluoride, as well as processes that indicate their failure, and the timing of their occurrence, is of theoretical and practical importance for developing recommendations for the timely prevention and correction of pathological conditions developing in employees of the aluminum and coal industry.The authors declare no conflict of interests.

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