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

Author(s):  
Anna G. Zhukova ◽  
Maria S. Bugaeva ◽  
Anastasiya S. Kazitskaya ◽  
Oleg I. Bondarev ◽  
Nadezhda N. Mikhailova

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.

Author(s):  
A. G. Zhukova ◽  
L. G. Gorokhova ◽  
A. S. Kazitskaya ◽  
T. K. Yadykina ◽  
N. N. Mikhailova ◽  
...  

Introduction. Fluorine compounds in small doses, but with prolonged exposure, cause various disorders in organs at the cellular and molecular levels. Activation of free-radical processes plays an important role in the damaging eff ect of fl uorides. Th erefore, one of the most eff ective ways to limit fl uorine-induced damage is to directly aff ect free-radical processes using herbal preparations with antioxidant properties.The aim of the study is to study the eff ect of a dihydroquercetin-based drug on the activity of free radical processes in brain tissue under subchronic exposure to sodium fl uoride (NaF).Materials and methods. Th e work was performed on white male laboratory rats weighing 200-250 g. Th e rats were divided into 3 groups: 1 — control; 2 — rats with chronic exposure to sodium fl uoride (NaF) for 9 weeks; 3 — rats receiving a NAF solution with simultaneous administration of a complex drug based on dihydroquercetin at a dose of 3 mg/kg in 1% starch gel for 3, 6 and 9 weeks. The activity of free radical oxidation and antioxidant defense enzymes — superoxide dismutase (SOD) and catalase-was determined in the cerebral cortex. Th e level of expression of hypoxia-induced transcription factor HIF — 1A and inducible forms of proteins HSP72 and HSP32 were determined in the cytosolic fraction of brain tissue.Results. In the early stages of subchronic fl uoride exposure (1-3 weeks), the expression of protective proteins HIF-1α, HSP72, HSP32 and catalase was shown in the rat cortex, as a result of which the activity of free-radical processes was maintained at the control level. An increase in the timing of fl uoride intake to 9 weeks led to a decrease in antioxidant protection and signifi cant activation of free radical oxidation in brain tissue. Daily administration of a complex drug with dihydroquercetin for 3, 6 and 9 weeks to rats with subchronic fl uoride exposure led to a decrease in the severity of pro- and antioxidant balance disorders in the cerebral cortex. At the same time, the greatest protective eff ect of dihydroquercetin with fl uoride exposure was manifested by the 9th week of its administration.Conclusions. When subchronic intake of fl uorides in the body, the drug based on dihydroquercetin has a neuroprotective eff ect, which is manifested by an increase in the activity of antioxidant enzymes of fr ee radical oxidation and catalase and the resistance of the cortex to induced fr ee radical oxidation.


2021 ◽  
Vol 26 (2(49)) ◽  
pp. 11-22
Author(s):  
O. V. Ketsa ◽  
M. M. Marchenko ◽  
О. А. Samuliak

Introduction. The effect of laser irradiation on the body can lead to local tissue damage, which will be accompanied by changes in biochemical processes that occur in the kidneys. The direction of these changes is completely unclear, so the study of free radical oxidation of lipids and proteins as the main markers of oxidative stress in the body and their correction by ω-3 polyunsaturated fatty acids (PUFA) remains relevant. Aim.  To evaluate the intensity of lipid peroxidation and oxidative modification of proteins in the postnuclear fraction of rat kidneys under the action of laser irradiation and additional administration of ω-3 PUFA. Methods. The studies used white outbred rats, which were irradiated daily for 4 minutes with a laser diode with a wavelength of 650 nm, power of 50 mW in the abdominal cavity at a distance of 10 cm from the skin surface. The state of lipid peroxidation (LPO) was determined by the level of primary, secondary and final products. The intensity of oxidative modification of proteins (OMP) was evaluated by the level of carbonyl derivatives and protein SH-groups. To correct the prooxidant state, the animals were additionally injected with ω-3 PUFA. Results. Low-intensity laser irradiation has a destructive effect on the cell membranes of the kidneys, which is expressed by an increase in primary, secondary and final products of LPO in phospholipid extracts and an increase in the intensity of OMP. The introduction of ω-3 PUFAs reduces free radical processes in the kidneys of irradiated rats, but this effect depends on the scheme of their introduction. ω-3 PUFAs do not show antioxidant effect under the conditions of their introduction after laser irradiation. Daily administration of ω-3 PUFA two hours before irradiation shows a slight antioxidant effect only in the initial stages of irradiation. Preliminary seven-day administration of ω-3 PUFA before laser irradiation is the most effective, as it helps to reduce free radical processes. Conclusion. It is established that ω-3 PUFAs are able to have a corrective effect on the action of low-intensity laser irradiation, which depends on the scheme of their introduction. The highest antioxidant effect is observed in groups of animals to which ω-3 PUFA was previously administered before the action of laser irradiation.


2016 ◽  
Vol 62 (4) ◽  
pp. 426-430 ◽  
Author(s):  
A.P. Gureev ◽  
M.L. Shmatkova ◽  
V.Yu. Bashmakov ◽  
A.A. Starkov ◽  
V.N. Popov

Fenofibrate is a synthetic ligand for peroxisome proliferator-activated receptors subtype alpha (PPARa); it is used for the treatment of a wide range of metabolic diseases such as hypertriglyceridemia, dyslipidemia, diabetes and various neurodegenerative diseases. We have studied the effect of fenofibrate on b-oxidation of fatty acids and related free-radical processes. The most effective concentration of fenofibrate (0.3%) added to the chow caused a significant decrease of the body weight of mice. The data obtained by quantitative PCR demonstrated increased hepatic gene expression responsible for b-oxidation of fatty acids in peroxisomes and mitochondria. Enhancement of oxidative processes caused a 2-fold increase in the rate of reactive oxygen species (ROS) production, as evidenced by determination of the level of lipid peroxidation (LPO) products in the liver. Mitochondrial antioxidant systems are more sensitive to elevated ROS production, as they respond by increased expression of SOD2 and PRDX3 genes, than cytoplasmic and peroxisomal antioxidant systems, where expression of CAT1, SOD1, PRDX5 genes remained unaltered.


2020 ◽  
Vol 99 (7) ◽  
pp. 750-754
Author(s):  
Anna G. Zhukova ◽  
Natalya N. Zhdanova ◽  
Anastasiуa S. Kazitskaya ◽  
Nadezhda N. Mikhailova ◽  
Tat'yana G. Sazontova

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.


Author(s):  
M. S. Bugaeva ◽  
O. I. Bondarev ◽  
N. N. Mikhailova ◽  
L. G. Gorokhova

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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