Activation Of Free Radical Processes Research Articles

Adaptogenic correction of free radical processes in liver tissue under the exposure to coal-rock dust on the body (experimental study)

Introduction. Damage to the liver under the conditions of long-term exposure to coal-rock dust on the body leads to significant impairment of its metabolic, detoxification, synthetic, and other functions. In this regard, it is relevant to search for early methods of prevention and correction of developing pathological changes in this organ. The purpose of the study is to experimentally study the effect of a complex drug with dihydroquercetin on the activity of free radical processes in the liver of laboratory rats over the dynamics of long-term exposure to coal-rock dust. Materials and methods. The work was carried out on male white rats weighing 200–250 g. The control group was kept under the standard vivarium conditions. The experimental group included rats that inhaled coal-rock dust in a priming chamber daily for 4 hours for 1, 3, 6, and 9 weeks and rats that received a daily complex drug with dihydroquercetin immediately before dust exposure. In the liver tissue, the activity of free radical oxidation and antioxidant defense enzymes (superoxide dismutase and catalase) was determined. Results. Priming rats with coal-rock dust for three weeks led to the gain in the intensity of free radical processes in the liver tissue: the initial level of accumulation of TBA-active oxidation products reliably raised by almost 2 times over the 1st week and 3 times over the 3rd week of the experiment compared to the control. An increase in the intensity of free radical oxidation was accompanied by activation of antioxidant defense enzymes - catalase - by 2.4 times at the 1st week and 1.6 times at the 3rd week of dust exposure. Raising the period of priming with dust up to 9 weeks led to multidirectional changes in oxidative metabolism in the liver tissue: at week 6, a decrease in the activity of superoxide dismutase was almost 3 times; at week 9, to a slight activation of antioxidant enzymes: superoxide dismutase by 55% and catalase by 36%.The most effective use of a complex drug with dihydroquercetin had been shown in short-term mode for three weeks, but not long-term (more than 6 weeks). The maximum antioxidant defense effect of dihydroquercetin was detected at the 3rd week of dust exposure – the level of free radical products decreased by 2 times and the activity of superoxide dismutase increased by 4 times. Limitations. Since the issue of organ-specific effects and the optimal duration of use of dihydroquercetin to increase resistance to free radical damage has been little elaborated, this imposes certain restrictions on its use for the correction and prevention of occupational diseases. Conclusion. The results obtained should be taken into account with long-term use of exogenous antioxidants in the correction and prevention of occupational diseases to support the level of endogenous antioxidant systems in the cell and the protective effect of dihydroquercetin for tissues most sensitive to the action of free radical processes.

Parameters of oxidative, nitrasive and anti-oxidative status in men with erectile dys-function due to combat trauma

The development of oxidative and nitrative stress and the processes of free radical oxidation are associated with many pathological processes. Damage of any origin leads to the activation of free radical processes not only in the place of damage, but also in the whole organism. The aim of the study is to assess the state of lipid peroxidation, content of GSH and GSSG and the activity of NO-synthase and arginase in lymphocytes and peripheral blood serum in men with erectile dysfunction due to combat trauma. The research was conducted on peripheral blood lymphocytes of men injured as a result of combat operations (shrapnel and bullet wounds) in the Russian-Ukrainian war, and who were treated at the Military Medical Clinical Center of the Western Region (Lviv, Ukraine). The research group of men with combat injuries was divided into two age groups: men aged 20–39 years and men aged 40–53 years. The MDA content in the blood serum of patients of both age groups was 1.35 times higher than in the control group. In peripheral blood lymphocytes, the MDA content in patients of the young age group was 1.27, and in patients of the middle age group in 1.39 times higher than in the control group. Simultaneously, no significant changes in the concentration of oxidized glutathione in blood serum and blood lymphocytes were found between men with erectile dysfunction due to combat trauma and healthy men. GSH content in blood serum in patients of both age groups was significantly lower than in the control group. The arginase/NOS ratio in blood serum was 9.75 times lower in the young age group and in 20.45 times lower in the middle age group compared to healthy men. It was established that in the blood serum and blood lymphocytes of men with erectile dysfunction due to combat trauma, processes of lipid peroxidation were intensified and the GSH level was reduced. The GSH/GSSG ratio was reduced only in blood serum. It was found that the oxidative stress is associated with development of nitrative stress. The arginase/NOS ratio was shifted towards increased NOS activity. Activation of iNOS was accompanied by significant inhibition of cNOS. Further study of biochemical mechanisms is important to understand the triggers of erectile dysfunction due to combat trauma.

Methabolic reaction on the cerebral ischemia during carotid artery surgery

One of the ischemic stroke prevention methods is reconstructive surgery on the carotid arteries, during which there is a risk of ischemia-reperfusion phenomenon. Nevertheless, there is still a high risk of stroke at all stages of the surgery, which equally depends on the atherosclerotic plaque structure and on the technique and tactics of surgery. The aim of this study was to investigate the dynamics of redox homeostasis and nitric oxide production in the blood taken from the internal jugular vein in patients with carotid arteries pathology against the episode of cerebral blood flow restriction during carotid surgery. This prospective cohort study involved 56 patients which required carotid reconstructive surgery. The markers dynamics of oxygen metabolism, redox homeostasis and nitric oxide production in blood from the internal jugular vein on the side of surgery were studied. It was found that the activity of free radical processes is proportional to the level of jugular hypoxemia. Bidirectional dynamics of lactate concentration during intraoperative transient cerebral ischemia was revealed. In some patients, lactate production activates with an increase in free radical processes activity in proportion to the intensification of nitric oxide synthesis against a decrease in peroxynitrite production and activation of molecular compensatory mechanisms increasing concentrations of L-arginine and reduced glutathione. In others, the extraction of oxygen from the blood increases without lactate production, activation of nitric oxide synthesis and development of oxidative stress. This indicates good adaptive reserves against acute restriction of cerebral blood flow.

Adaptive reactions of wheat plants to drought conditions under the influence of salicylic acid

Background. Drought is one of the most important factors affecting plant growth and productivity. The study addressed the perspectives of usage of salicylic acid, a stress protective compound, to increase the adaptive potential of Triticum aestivum L. plants under drought conditions. The effect of salicylic acid on the photosynthetic apparatus of wheat plants under the conditions of drought with a subsequent gradual resumption of watering was investigated. Materials and methods. Plants of the Podolyanka variety of wheat (Triticum aestivum L.) were the objects of our study. Seeds were pre-soaked in a solution of salicylic acid (50 mM) for 3 h. First seeds germinated in an incubator, and on the 3rd day of growth were transplanted into plastic pots (d = 14 cm). Plants were grown on soil substrate, whose humidity was maintained at 60 % of full moisture capacity – the optimal water supply. The model of drought was created by the simultaneous cessation of irrigation (30 % of soil moisture capacity) for 12 days. Upon termination of the drought, soil moisture in the pots was adjusted to 60 % of its full capacity. The control plants were grown from the seeds not treated with salicylic acid under conditions of optimal water supply (60 %). Study samples were taken from the shoots of wheat on the 7th, 9th and 12th days of the drought period and on the first day after the resumption of irrigation (14 days). The concentrations of TBA-active products, chlorophyll, carotenoids, glucose, sucrose and chlorophyllase activity were determined. Results. The influence of salicylic acid on the content of chlorophyll, carotenoids and TBA-active products along with chlorophyllase activity in shoots of wheat under the drought conditions on the early stages of ontogenesis was determined. It was found that both drought and salicylic acid modify the content of chlorophyll and carotenoids in the shoots of Triticum aestivum L., apparently by altering their metabolism. Chlorophyllase plays an important role in the adaptation of photosynthetic apparatus to the drought conditions. Our results suggest that salicylic acid causes an increase in the content of photosynthetic pigments and a decrease in chlorophyllase activity in drought conditions. In addition, salicylate causes the accumulation of glucose and sucrose in the shoot tissues of wheat plants under stressful conditions. Conclusions. Our research suggests participation of salicylic acid in the plants’ adaptation processes under the conditions of moisture deficiency. It was also found that under the effect of salicylic acid the content of TBA-active products decreases in the plant shoots under the conditions of drought. Considering the fact that the content of TBA-active products is an important indicator of lipid peroxidation intensity, the decrease of this index reveals the reduced activity of free radical processes in plant tissues under the effect of salicylic acid. Thus, it can be assumed that SA has a positive effect on plant metabolism under drought conditions.

Morphological and functional changes in rat thyroid gland after a year following chronic exposure to low and intermediate doses of γ-radiation

Introduction Thyroid function depends on iodine uptake by the body as well as on exposure to various harmful environmental hazards (stress, ionizing radiation). Aim The aim of the work was to assess the effect of exposure to low and intermediate doses of external γ-radiation on the thyroid structure and function in young female rats at remote periods after radiation. Materials and Methods Forty female rats were used to study remote effects of external γ-radiation exposure during 20 d (at daily doses of 0.1, 0.25 and 0.5 Gy) on the functional activity (levels of thyroid hormones, iodine metabolism) and the morphological structure of the rat thyroid) after 12 months following the radiation exposure. Results An increase in thyroid mass and a decrease in total thyroid protein concentration along with a reduction of blood T3 and T4 was shown only in rat groups exposed to 0.25 and 0.5 Gy. Both the concentration of total iodine and its protein-bound fraction (1.2–1.4 fold, p < .01) and the protein-bound to total iodine ratio were decreased in the thyroids of all irradiated animals. The 0.1-Gy group showed elevated thyroperoxidase (TPO) activity along with increased catalase activity, which may indicate the activation of iodine oxidation by thyrocytes. Only the 0.5-Gy group demonstrated reduced urinary excretion of iodine (2.1 fold, p < .01). The reduction of thyroid function at radiation doses of 0.25 and 0.5 Gy was characterized by a microfollicular structure and the development of atrophic changes in the parenchyma, desquamation of thyroid epithelium and an increase in epithelium proliferation. The diameter of the thyrocyte nuclei was increased in rats exposed to 0.25 and 0.5 Gy, which indicates functional tension of thyrocytes. Conclusion Our research shows that after a year, the exposure to external γ-radiation of 0.1, 0.25 and 0.5-Gy caused changes in the structure and function of the rat thyroid which are manifested by the development of hypothyroiditis (0.5 Gy), ‘subclinical’ hypothyroiditis (0.25 Gy) and functional tension of thyrocytes. The mechanisms of thyroid dysfunction - impaired- uptake of iodine and its organification against the background of activation of free radical processes – suggest disturbances in the function of the sodium/iodide symporter (NIS), TPO and thyroglobulin synthesis. In contrast to the intermediate doses, the effects of the 0.1-Gy dose were mostly found at the remote periods compared to the earlier periods (180 days).

Dynamics of free radical processes in the oral fluid of patients with chronic recurrent aphthous stomatitis at the first stage of therapy

Chronic recurrent aphthous stomatitis (CRAS) is a disease of the oral mucosa, characterized by the appearance of specific round aphthous forms with hyperemic corolla, covered with grayish-yellow plaque against the background of inflamed mucous membrane, which violates the oxidative homeostasis of oral fluid and the body as a whole.The aim of our study was to reveal the dynamics of free radical processes in oral fluid of patients with chronic recurrent aphthous stomatitis on the background of the first stage of antiseptic therapy with analgesics in order to determine the optimal treatment tactics for this condition. In order to achieve the set objective we had to solve the following tasks: to evaluate the functional activity of free radical processes in the oral liquid of patients with CPAS on the background of antiseptics (chlorhexidine, octenisept, furacilin, myramistine) and anaesthetic (Camistad gel) application for 7 days.Materials and Methods. During the study the oral fluid of 120 people diagnosed with CPPS was studied, divided into 4 groups equally: Group 1 – control, patients used the antiseptic chlorhexidine for gargling; Group 2 – patients with CPPS therapy with octenisept; Group 3 – patients with CPPS therapy with furacilin; Group 4 – patients with CPPS therapy with miramistine. For pain relief, patients in all groups used Kamistad gel. Analysis of free radical processes in oral fluid of patients was carried out before the study and on the 7th day of therapy by determining products of oxidative modification of biomolecules on the basis of quantitative evaluation of stained complex with thiobarbituric acid (TBA), maximal flash (MVHL) and area (PCL) of H2O2-induced luminol-dependent chemiluminescence using LT-01 chemiluminometer ("Horos" "Joint Venture Soviet-Swedish Company"). Concentration of diene conjugates and malonic dialdehyde was also determined to estimate enzymatic part of oxidative homeostasis.Results of the study. Results of the researches permit to conclude that at chronic recurrent aphthous stomatitis enzymatic activity of an oral liquid changes. According to the presented data the initial values of concentration of TBK-RP, maximal flash of oral chemiluminescence, area of oral chemiluminescence and concentration of MDA and DC in the control group and three experimental groups reliably differ from the data received on the 7th day of the research. Significant decrease of the studied indexes of oral liquid testifies to the efficiency of the first stage of therapy of aphthous stomatitis by antiseptic preparations and decrease of intensity of oxidative processes in oral liquid. Of all the proposed antiseptics the best efficiency is demonstrated by octenisept, reliably worse are chlorhexidine and myramistine and the least effective in the therapy of CPAS is furacilin.Conclusions: treatment of CPAS with Octenisept in combination with Camistad gel is the most effective in restoration of the disturbed oxilite.

Interrelation between the parameters of endogenous vascular regulation, oxidative stress and the markers of inflammatory response in COVID-19 patients while on extracorporeal membrane oxygenation

Introduction. Extracorporeal membrane oxygenation has found wide application in clinical practice during the COVID-19 pandemic. Oxidative stress, endothelial dysfunction, and systemic inflammatory response syndrome play an important role in the pathogenesis of COVID-19. Our research was designed to study correlations in-between those factors and the impact of extracorporeal membrane oxygenation on them.Aim. The study of systemic inflammatory response and endothelial function in patients with COVID-19 during extracorporeal membrane oxygenation.Material and methods. In the course of a prospective study, we examined 100 COVID-19 patients aged 26 to 75 years, median 55 years [47;60], who were treated at the N.V. Sklifosovsky Research Institute for Emergency Medicine, using extracorporeal membrane oxygenation. As a control group (normal), 25 practically healthy people whose median age was 32 years [25;39] were examined. The function of the vascular endothelium was assessed by the content of nitric oxide stable metabolites in the blood serum and the level of angiotensin-converting enzyme. Next, the ratio of nitric oxide metabolite to angiotensin-converting enzyme level was calculated, reflecting the imbalance between endotheliumdependent vasodilation and vasoconstriction. To assess the severity of oxidative stress in blood serum, malondialdehyde was determined as a marker of lipid peroxidation. The state of the antioxidant system was assessed in terms of total antioxidant status of blood serum. The presence of an imbalance in the system of lipid peroxidation and the antioxidant system total antioxidant status was judged by the oxidative stress coefficient, i.e. the ratio of malondialdehyde to the total antioxidant activity.Results. The analysis showed the presence and progression of endothelial dysfunction, impaired vascular regulation, activation of free radical processes, the presence of an imbalance in the prooxidant/antioxidant system, as well as the progression of the inflammatory process with a decrease in the level of markers of the COVID-19 severity.Conclusion. Further studies of the correlation between endothelial damage and the severity of the systemic inflammatory response syndrome may be of fundamental importance for explaining the pathophysiological mechanisms of COVID-19 course and developing new treatments for such patients.

ЕКСПРЕСІЯ ГЕНІВ LRP1 ТА OLR1 У КРОВІ ХВОРИХ НА ОСТЕОАРТРИТПІСЛЯ SARS-CoV2-ІНФЕКЦІЇ

Background. Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection was first reported in Wuhan, China in December 2019, and then spread rapidly worldwide, causing an estimated 771 million active cases with ~7 million deaths as of September 2023. The pandemic of the new coronavirus SARS-CoV-2 poses a great threat to the world in many aspects: medical, social, economic and other. A comprehensive understanding of the interaction of the virus with the body is fundamentally important in the fight against SARS-CoV-2. During the 2019 coronavirus disease (Coronavirus disease 2019, COVID-19), epithelial cells of the respiratory tract are affected, which is manifested by symptoms of a respiratory infection. The SARS-CoV-2 virus, as an infectious trigger, causes damage to other organ systems, in particular, the musculoskeletal system, and can also complicate the condition of patients with comorbid diseases. Мethods. The aim of the work was to determine the expression of LRP1 and OLR1 genes in the blood of patients with osteoarthritis after SARS-CoV2 infection. All study participants were divided into three groups. The first group (n = 10) is conditionally healthy people. The second group (n = 22) – patients with osteoarthritis of the knee joints II-III degree. The third group (n = 14) is patients with osteoarthritis of the knee joints II-III degree, who suffered a mild and moderate form of COVID-19 6–9 months ago. The expression of LRP1 and OLR1 genes was determined in the blood. RNA was obtained by the Chomczynski method. Synthesis of cDNA and quantitative polymerase chain reaction in real time (Real-time PCR, qPCR) using the commercial kit "Thermo Scientific Verso SYBR Green 1-Step qRT-PCR ROX Mix" ("Thermo Scientific, Lithuania). Processing of research results was carried out using generally accepted methods of variational statistics. Results. In the blood of patients with osteoarthritis, the expression of the LRP1 gene decreases and the expression of the OLR1 gene increases compared to a group of conditionally healthy people. In patients with osteoarthritis after infection with SARS-CoV-2, more significant violations of the expression of the studied genes are shown. Conclusions. The obtained data indicate a violation of the metabolism of lipoproteins in the body, the activation of free radical processes and the development of systemic inflammation, which leads to a decrease in vascular protection and endothelial dysfunction in patients with osteoarthritis, which increases under conditions of additional infectious load on the body under the influence of SARS-CoV2 infection.

Association of HIF-1A (rs11549465) gene polymorphism with congenital malformations and intrauterine growth retardation of the fetus

Introduction. Congenital malformations have long received the status of a marker of environmental distress. Six per cent of the newborns in the world are diagnosed with congenital malformations of various etiologies, 30 million develop intrauterine growth retardation, often associated with hypoxia, while the number of these pathologies is significantly higher in environmentally unfavourable regions. The degree of resistance to hypoxia is determined by the transcription factor induced by hypoxic conditions - HIF. There is revealed polymorphism of the HIF gene, which determines the differences in the activity of the transcription factor encoded by this gene, and therefore, the differences in the level of resistance to hypoxia. Recently, HIF has also been detected in response to the activation of free radical processes. Materials and methods. The study examined fifty five women living in the South of Kuzbass, most of them in the city of Novokuznetsk. 18 women were included in the control group because they carried a healthy child, the study group consisted of 11 women who gave birth to children with intrauterine growth retardation, and 26 women who gave birth to children with congenital malformations. Genomic DNA was isolated from peripheral blood leukocytes using the phenol-chloroform extraction method. Gene typing was carried out by the Real Time method. Results. Among the studied groups, in women who gave birth to children with congenital malformations, there were no reliable differences in the occurrence of polymorphisms of mutant and wild types. In the group of women who gave birth to children with intrauterine growth retardation, a reliable association of C/T polymorphism in the mother with intrauterine fetal growth retardation was shown (χ2 = 4.54; OR = 9.71), while the ancestral form of C/C was associated with resistance to this pathology. Limitations. Since the identification of the association of the HIF-1A (rs11549465) gene polymorphism with intrauterine growth retardation was of a pilot nature, it is advisable to increase the sample. Conclusion. The results obtained may indicate the leading role of the HIF-α subunit in the body’s adaptation to hypoxia and the secondary importance of this protein in the regulation of pro- and antioxidant balance.

Стан тканин пародонта у щурів на тлі їх тривалої алкоголізації

The aim of our research is to study the condition of periodontal tissues of rats against the background of prolonged alcoholism. The studies were performed on 19 white nonlinear rats weighing 180-220 g, which were randomly divided into 2 groups. Rats of the first group served as controls. They were injected intragastrally with saline for 72 days. The rats of the second group for 72 days were intragastrically injected with increasing concentrations of ethanol according to the following scheme: 1-24 days - 11.8%; 25-48 - 23.6%; 49- 72 days - 37%. In rat soft periodontal tissues, free fucose content as a monomer of fucoproteins, glycosaminoglycans as proteoglycan heteropolysaccharides, total proteolytic activity, total antitryptic activity, TBA-active products, oxidatively modified proteins and catalase activity was determined. 72- day alcoholization of rats caused an increase in periodontal tissue content of TBA-active products by 74.7%, the content of oxidatively modified proteins by 28.9% and catalase activity by 33.3%, indicating the activation of free radical processes. At the same time, the total proteolytic activity in periodontal tissues decreased by 20.6% against the background of a decrease in the activity of proteinase inhibitors by 9.6%. Also, under conditions of long-term administration of ethyl alcohol to animals an increased depolymerization of fucoproteins and proteoglycans of periodontal connective tissue was observed, as evidenced by an increase in free fucose content by 37.5% and glycosaminoglycans 175.4%. Under conditions of longterm administration of ethyl alcohol to rats, an increased depolymerization of fucoproteins and proteoglycans of periodontal connective tissue is observed, which plays a leading role in the fixation and stability of teeth.

Study of effect of Astragalus vulpinus extract on lipid peroxidation processes in hypothalamic region on lipopolysaccharide immune stress model

An experimental study is devoted to the study of the effect of Astragalus vulpinus extract on lipid peroxidation processes in the hypothalamic region under conditions of lipopolysaccharide immune stress. Material and methods. Experiments were performed on white male rats 6-8 months of age. In all series of experiments, animals were divided into groups (n = 10): 1st – control individuals receiving distilled water in an equivalent volume; 2nd – rats with immune stress model; 3rd – individuals treated with Astragalus vulpinus extract against the background of immune stress. The test extract and distilled water were administered once a day intragastrically with a 50 mg/kg probe for 14 days. Immune stress was formed by single intraperitoneal administration of lipopolysaccharide pyrogenal isolated from Salmonella typhi microbial cells. The intensity of free radical oxidation processes was studied by thiobarbituric acid reactive substances (TBARS) content, spontaneous and ascorbate-dependent lipid peroxidation rate and catalase activity were also determined. Results. According to the results of the experiment, it was revealed that immune stress is accompanied by the activation of free-radical oxidation processes, as evidenced by an increase in the concentration of products of this process and the activity of the body’s antioxidant protection enzyme catalase. Assessment of the effect of Astragalus vulpinus herb extract on the free radical potential in the hypothalamic region against the background of the action of lipopolysaccharide-induced immune stress showed that the studied extract exhibits pronounced stress-protective and antioxidant properties characterized by changing the intensity of lipid peroxidation processes and by increase of catalase activity in the tissue of the hypothalamic brain region. Conclusions. Astragalus vulpinus herb extract has been proven to exhibit antioxidant effects by restoring activity of free radical processes.

Effects of Panthenol and N-Acetylcysteine on Changes in the Redox State of Brain Mitochondria under Oxidative Stress In Vitro.

The glutathione system in the mitochondria of the brain plays an important role in maintaining the redox balance and thiol–disulfide homeostasis, whose violations are the important component of the biochemical shifts in neurodegenerative diseases. Mitochondrial dysfunction is known to be accompanied by the activation of free radical processes, changes in energy metabolism, and is involved in the induction of apoptotic signals. The formation of disulfide bonds is a leading factor in the folding and maintenance of the three-dimensional conformation of many specific proteins that selectively accumulate in brain structures during neurodegenerative pathology. In this study, we estimated brain mitochondria redox status and functioning during induction of oxidative damage in vitro. We have shown that the development of oxidative stress in vitro is accompanied by inhibition of energy metabolism in the brain mitochondria, a shift in the redox potential of the glutathione system to the oxidized side, and activation of S-glutathionylation of proteins. Moreover, we studied the effects of pantothenic acid derivatives—precursors of coenzyme A (CoA), primarily D-panthenol, that exhibit high neuroprotective activity in experimental models of neurodegeneration. Panthenol contributes to the significant restoration of the activity of enzymes of mitochondrial energy metabolism, normalization of the redox potential of the glutathione system, and a decrease in the level of S-glutathionylated proteins in brain mitochondria. The addition of succinate and glutathione precursor N-acetylcysteine enhances the protective effects of the drug.

New data on well-known drug: focus on meldonium

The article reviews the efficacy of meldonium in patients with various diseases, which are based on secondary mitochondrial dysfunction. Mitochondria are complex cellular organelles that control many metabolic processes, including fatty acid oxidation, the Krebs cycle, oxidative phosphorylation in the electron transport chain, and many other processes. Many conditions can lead to secondary mitochondrial dysfunction and affect other diseases. Damage to mitochondria can promote the activation of free radical processes and the initiation of the mechanisms of programmed cell death, mitochondrial dysfunction decrease in the immune response, increase in the activity of the body’s inflammatory response in various infections. Mitochondria appear to be important in COVID-19 pathogenesis because of its role in innate antiviral immunity, as well as inflammation. The article presents data on the effectiveness of using meldonium as a drug that helps to arrest pathological processes in mitochondria. The main mechanism of action of meldonium is based on a decrease in L-carnitine levels and increase of peroxisomes activity in the cytosol Meldonium was designed as a inhibitor of carnitine biosynthesis aimed to prevent accumulation of cytotoxic intermediate products of fatty acid beta- oxidation in ischemic tissues and to block this highly oxygen- consuming process. It is based on the correction of the energy metabolism of the cell. There was a positive trend in the use of meldonium in patients with diseases of the cardiovascular system (chronic ischemic diseases, chronic heart failure, arterial hypertension, etc.), neurological disorders (stroke, cerebrovascular insufficiency, etc.), respiratory diseases. The data on the beneficial effect of meldonium on the immune response in patients with coronavirus, bronchial asthma, chronic obstructive pulmonary disease, during vaccination with anti-influenza serum are presented. A decrease in asthenia was noted against the background of the use of meldonium in patients who had undergone coronavirus infection.

Pathogenetic rationale for using an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and an antioxidant coenzyme Q&lt;sub&gt;10&lt;/sub&gt; in the treatment and prevention of cardiovascular disease

The review discusses atherosclerosis-related mechanisms of car-diovascular disease development, as well as the optimization of their prevention and treatment methods. Recent experimental and clinical studies have shown the important role of vascular endothelium in the development and progression of atherosclerosis. Myocardial ischemia, activation of free-radical processes and impaired bioenergetics initiate a decrease in production of nitric oxide, which plays major vasodilator role. In this regard, the scientists is interested in the search for new drugs that can affect the main pathogenetic links of coronary artery disease. Statins are currently the drugs of choice. However, they are not always effective and have an ambiguous effect on oxidative potential of myocardial cells and endothelial function. Moreover, inhibition of mevalonic pathway for cholesterol synthesis is accompanied by a deficiency of coenzyme Q10, which is the central cellular antioxidant that protects phospholipids of cell membranes from free radicals. Rationale of using coenzyme Q10 in the complex treatment and secondary prev ention of cardiovascular diseases, including coronary artery di sease, is discussed.

Activity of free radical processes in oral fluid of patients with recurrent upper respiratory tract infections

Background: Upper respiratory tract infections occupy a leading position in the infectious pathology. According to the World Health Organization (WHO), up to 500 million people fall ill with acute respiratory infections in the world every year, of which 2 million people die from various complications. At the same time, a number of researchers note the lack of methods for clinical and laboratory assessment of the condition of patients with this pathology. Aims: To evaluate the parameters of free radical oxidation in oral fluid of patients with recurrent upper respiratory tract infections (RIURT). Methods: The study involved 64 apparently healthy people who suffered respiratory infections up to 2 times a year, and 85 patients with RIURT (4 or more times a year), who at the time of the study were in remission. The determination of the parameters of the pro / antioxidant systems was carried out using two methods (photometric: the content of lipid peroxidation products and the level of ceruloplasmin and luminol-dependent chemiluminescence (LDCL) were measured, making it possible to assess the complex interaction of two systems prooxidants and antioxidants). Results: The studies have demonstrated that, for most of the RIURT patients during remission, the levels of certain prooxidant components (diene conjugates, ketodienes, Schiff bases), as well as of an oral fluid antioxidant (ADS: ceruloplasmin) were elevated compared to the controls. At the same time, the LDCL parameters of oral fluid did not go beyond the reference interval, although they were changed relative to the median of the control group. This allows us to consider the observed fluctuations as a balance in the system of pro- and antioxidants. Conclusions. The use of oral fluid as a biological material for the assessment of the pro-/antioxidant system opens up new possibilities in the diagnosis of respiratory disease.

Activity of free radical oxidation processes in rats with paracetamol hepatitis and correction with shiitake mushrooms thick extract

The antioxidant defense system controls and inhibits all stages of free radical formation reactions, which start from their initiation and end with the formation of hydroperoxides and malonic dialdehyde. Disorders of the body's antioxidant defense system can be caused by both endogenous and exogenous factors and can lead to the oxidative stress development. For the purpose of the negative impact minimizing and correction of the existing disorders, both natural and synthetic origin antioxidants are used. Preference is given to antioxidants of natural origin, due to their mild action and minimal side effects.&#x0D; Shiitake mushrooms are known in China and Japan as a product that has nutritional and medicinal value, for thousands of years. They contain an extremely rich complex of various biologically active substances that can have antioxidant, hepatoprotective effect and influence on the liver diseases pathogenesis.&#x0D; The aim of the work was to investigate the effect of shiitake mushrooms thick extract on the activity of free radical processes and indicators of the antioxidant system under the conditions of paracetamol hepatitis in rats.&#x0D; The experimental work was being conducted on the white male rats, which were divided into 10 groups of 6 animals each. Acute hepatitis was simulated by intragastric administration of paracetamol in a dose of 1 250 mg/kg 1 time per day (for 2 days) as a suspension in 2% starch gel solution. We investigated the effect of shiitake mushrooms thick extract on the induced pathology, which was administered intragastrically 2 hours before the paracetamol introduction and daily after the lesion in a dose of 150 mg/kg of the rat’s body weight. Silibor was selected as the comparison drug, which was administered according to the same scheme like the investigated extract in a dose of 20 mg/kg of the animal’s body weight. Euthanasia was conducted on the 3rd, 7th and 10th day after the onset of the lesion. Liver homogenate and animal serum were examined. The effectiveness of shiitake mushrooms thick extract was evaluated under the conditions of the caused pathology by superoxide dismutase and catalase activity, as well as by the content of TBA-active and proteins oxidative modification products.&#x0D; An increasing of the TBA-active products content and the products of proteins oxidative modification in the serum and liver of animals after the toxic paracetamol exposure testifies to the liver damage and the development of acute hepatitis in rats. Decreased activity of antioxidant enzymes such as catalase and superoxide dismutase was also noted.&#x0D; An investigation, which was conducted by us, allowed us to reveal a positive effect of shiitake mushrooms thick extract on the activity of lipoperoxidation and oxidative modification of proteins under the conditions of white rats paracetamol lesion.

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

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.

Effect of second-hand smoke on the immunological parameters of wistar rats and their offspring

The literature covers multiple negative effects of active and passive tobacco smoking upon the human body and experimental animals. Much lesser attention is given to the features of the immune system in offspring from the passively smoking experimental animals. In previous works, we studied physiological and immunological parameters in the infant rats born from passively smoking rats. The present work expands the scope of this direction and is devoted to assessment of immunological parameters in passively smoking pregnant rats and their offspring. Quantitative determination of immunological parameters was carried out in pregnant Wistar rats exposed to passive tobacco smoking and in 65 pup rats from smoke-exposed and nonexposed animals. The experimental rats were exposed to tobacco smoke for 8 hours from the 1st to the 20th day of pregnancy. In all animals, the body weight, thymus and spleen, the number of white blood cells, thymocytes, splenocytes, and myelocaryocytes were determined. On the 20th day of pregnancy, the smoking rats showed a significant decrease in the weight of animals, the number of thymocytes and myelocaryocytes. A decreased body mass of animals and their thymus glands, lower number of thymocytes were registered in pup rats born from smoking females as compared with control animals. These changes in immunological parameters may be based on a number of possible reasons. On the one hand, tobacco smoke promotes activation of free-radical processes with a simultaneously decreased efficiency of antioxidant mechanisms. This activation may result from exposure to the components of tobacco smoke, in particular, chromium, as a metal of variable valence, as well as benzene, which is transformed by the free-radical oxidation mechanisms. On the other hand, some tobacco smoke components may promote apoptosis which plays a significant role in the cellular exhaustion of immunogenesis system. Moreover, a decreased number of thymocytes may be caused by their migration from cortical areas to the medulla, followed by release into bloodstream. Thus, the results obtained indicate that the detected changes in these parameters are more pronounced in pregnant rats who were exposed to tobacco smoke and their offspring, and expand the knowledge of changes in the immune system in the offspring of passively smoking animals. The presented data may present a basis for development of drugs that reduce toxic effect of ecotoxicants, including passive tobacco smoking.

To the Mechanism of Adrenaline Damage to the Heart Tissue and the Mechanism of Cardioprotection by Neonatal, Xenogenic, Cardiac Cells. Dynamics of Creatine Phosphate, Lactate and Malondialdehyde

The development of disturbances in energy processes and damaging free radical reactions in various pathological processes, including cardiovascular diseases, are interrelated and lead to a significant deterioration in the course of diseases. Aim of the study . Research of the dynamics of malondialdehyde, creatine phosphate and lactate in the cardiac tissue of rats under experimental adrenaline stress and during its correction with neonatal, xenogenic, cardiac cells. Methods . The experiment was carried out on outbred male rats. Adrenaline damage to the heart was simulated by a single subcutaneous injection of 0.1% adrenaline solution at a dose of 0.5 mg per 100 g of body weight. The first group (37 rats) was injected subcutaneously with adrenaline, the second group (41 rats) – adrenaline and isolated heart cells of a newborn rabbit at a dose of 500 000. The third group included 6 healthy rats. Results . It was found that a spike in the level of malondialdehyde and, accordingly, the activation of free radical processes in adrenaline damage to the heart, occurred during the restructuring of the energy of the heart cell from intense glycolysis to the restoration of active mitochondrial ATP synthesis (which corresponded to the end of the depletion of lactate and creatine phosphate, and the beginning of the restoration of their content in heart cells). The dynamics of MDA sensitively reflected both the activity and the inhibition of oxidative processes in mitochondria, which manifested itself, respectively, both in the form of peaks and in a low level of MDA and corresponded to the interpretation of the dynamics of lactate and creatine phosphate. In the cardiac tissue of rats with transplantation of neonatal, xenogenic cardiac cells, the accumulation of lactate in the early stages of the experiment decreased, the subsequent depletion of the cellular reserves of creatine phosphate and lactate was inhibited, the period of inhibition (non-increase) in MDA was shorter, the subsequent increase in MDA was more moderate than in control animals. Conclusion . The data obtained indicate that neonatal cardiac cells are able to limit the disturbance of aerobic and of anaerobic processes in the heart tissue and promote the restoration of mitochondrial energy processes. Moreover, they contribute to a more efficient restoration of mitochondrial ATP synthesis, accompanied by a smaller burst of damaging free radical processes.

Modulating Oxidative Stress Indices and Thiol-Disulfide Balance in the Brain Structures by Pantothenic Acid Derivatives in an Experimental Model of Parkinson’s Disease

Abstract—We studied changes in the indices of free-radical oxidation and thiol-disulfide status in the brain structures in the experimental model of Parkinson’s disease (PD) induced by administration of rotenone to rats. Pantothenic acid derivatives, such as panthenol (PL), pantethine (PT), and homopantothenic acid (HPA) were used as neuromodulators. It was found that redox imbalance in the brain induced by rotenone is accompanied by the activation of free-radical processes, pronounced inhibition of antioxidant defense, a considerable decrease in the glutathione system reduction potential, and increased protein glutathionylation. The strongest changes were in the basal ganglia of the brain. PL and PT but not HPA, decrease the changes in the free-radical oxidation and thiol-disulfide balance in the brain structures. During experimental neurotoxicosis, the mechanisms of neuroprotective action of PL and PT, which are linked with the changes in the biosynthesis of CoA, are, obviously, related to their ability to increase the reduction potential of the glutathione system, thus mitigating the effects of oxidative stress.