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Introduction. Oxymethyluracil is an effective antihypoxant in a model of histotoxic hypoxia. Acetylcysteine combines the properties of a toxicotropic nonspecific and toxicokinetic antidote, promotes the synthesis of glutathione in the body. The aim of the research was a preliminary assessment of the antihypoxic properties of the complex compound of oxymethyluracil with acetylcysteine in the model of histotoxic hypoxia. Materials and methods. To study the antihypoxic properties, a model of acute histotoxic hypoxia was used. The studied compound was injected into the abdominal cavity of experimental mice three times with an interval of 30 minutes at 100 and 500 mg/kg of body weight, then after 30 minutes the toxicant was introduced. Comparators were oxymethyluracil and acetylcysteine. Results. The complex compound of oxymethyluracil with acetylcysteine in the model of acute histotoxic hypoxia statistically significantly was established to increase the lifespan of mice at a dose of 500 mg/kg of body weight. A dose of 100 mg/kg of the compound is practically ineffective. Limitations. The limitations of the study are related with antihypoxic properties of the new complex compound of oxymethyluracil with acetylcysteine previously studied in one model of hypoxia (histotoxic), because oxymethyluracil (as an antihypoxant) is most effective in this experimental model. For a final judgment on the antihypoxic properties of the studied compound, it is necessary to continue studies on other models of hypoxia. In addition, in order to identify possible synergism (potentiation) of the action of oxymethyluracil and acetylcysteine, it seems appropriate to conduct studies to evaluate the antihypoxic effect with their simultaneous administration (in the form of a simple mixture). Conclusion. A new complex compound of oxymethyluracil with acetylcysteine can be recommended for further wider (preclinical) research as a potential antihypoxant.

Introduction. There are a few effective therapies are available for acute liver injury at present. The aim of the study was to investigate histological and morphometric changes in the liver using models of toxic damage caused by carbon tetrachloride (CCl4 ) and acetaminophen during correction with Oxymethyluracil (OMU). Material and methods. A total of ninety rats were divided into 18 groups. The treatment of acute liver damage models caused by a single injection of CCl4 or acetaminophen was carried out using “Heptor”, “Mexidol”, and OMU. The correction was carried out twice (sacrificed 24 hours after intoxication) and four times (sacrificed 72 hours after intoxication). Liver tissues were processed using standard histological techniques (H&E). A semi-quantitative assessment was performed using a scale based on the severity of liver cell deaths. Results. Twenty-four hours after administration of CCl4 or 72 hours after administration of acetaminophen, the treatment with OMU led to a decrease in liver cell death compared to the group with administration of only CCl4 or acetaminophen. Seventy-two hours after CCl4 and 24 hours after acetaminophen intoxication, these groups with the OMU treatment did not differ from those of the carbon tetrachloride- or acetaminophen-induced liver injury groups, respectively. Conclusion. Thus, on the model of CCl4 liver injury, the treatment with OMU is more effective for 24 hours. In the case of acetaminophen intoxication, the effectiveness of treatment with OMU is better for 72 hours. The results obtained are possibly associated with a different mechanism of the damaging effect of the studied toxicants.

Aging is an individual, complex biological process, modulated by internal and external factors, characterized by a progressive loss of biological / physiological integrity, which leads to body dysfunction, increases vulnerability and death. Influence of activity type on aging rate has been convincingly shown in many studies, which makes it possible assess differences in aging rate of workers, exposed various occupational factors, conditions, work nature and intensity in certain professional and seniority groups, adequately reflects health state and can predict effectiveness of human labor activity. As integral indicator, it can help identify individuals at risk of age-related disorders, serving as a measure of relative fitness and predicting later life disability and mortality, regardless of chronological age. The article provides an overview of the main measuring ageing rate methods based on biomarkers, such as functional (“Kiev model”, WAI) and molecular genetic biomarkers (determination of telomere length, β-galactosidase enzyme activity) of human ageing, applicable in occupational medicine. The review discusses the main requirements for biomarker sets compilation, methods applicability and reliability, mathematical approaches to biological age calculating, and some workers biological age calculating problems. This allows assuming the great potential for using biological age to assess the impact of working conditions and work nature on workers’ ageing rate to prevent disability and improve quality of life.

Introduction. Considering the prevalence of acute alcohol poisoning in Russia, it seems urgent to search for new effective means of correcting them. Along with taking measures to remove ethanol from the body, pathogenetic correction is effective. Oxymethyluracil and its derivatives have proven to be effective hepatoprotectors in various experimental models of liver damage. The aim of the research was the evaluation of the effectiveness of oxymethyl uracil on the model of acute alcohol intoxication. Material and methods. On the model of acute toxic liver injury of laboratory animals with ethanol, the efficiency of correction of pathological changes with oxymethyl uracil was studied compared to the drug “Mexidol”. A complex of biochemical, morphological and genetic studies was carried out. Results. The morphological studies showed that the correction with oxymethyluracil was more effective at both time points than the drug “Mexidol”, which was manifested in a lower intensity of damage to the liver parenchyma. In the group that received oxymethyluracil, a restoration of the frequency of expression of the Chek 1 gene was observed both after 24 and 72 hours. Upon acute exposure to ethanol, a slight decrease in the level of RIPK1 gene expression was observed. The level of expression of this gene decreased most significantly during the correction of oxy methyl uracil. A decrease in the frequency of expression of this gene can indicate a slowdown in necrosis processes and suppression of reactive oxygen species production in liver cells and, consequently, a curative effect of oxymethyluracil in this type of intoxication. Conclusion. Based on the complex biochemical, morphological and genetic studies carried out, it can be concluded that under acute exposure to ethanol, the corrective effect of oxymethyl uracil is more pronounced than Mexidol (ethylmethylhydroxypyridine succinate).

The paper presents the results of studies of metabolic changes in the blood serum of rats on the background of oral administration of cadmium chloride for 2 months. Elevated serum hepatic enzymes are the main indicator of damage to hepatocytes caused by cadmium poisoning. It was shown that in three experimental groups of rats, which were intragastrically injected with CdCl2, the level of activity of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase was significantly increased compared to the control; on average, the increase in biochemical parameters was 31.8%, 12.9% and 21.9%, respectively. A decrease in the alkaline phosphatase activity in the blood serum of experimental animals, depending on the increase in the dose of the pollutant, is a consequence of the degree of heavy metal damage to the epithelium of the bile ducts. High levels of biochemical parameters of the renal profile, uric acid (UA) and urea, due to impaired glomerular filtration are shown. The noted decrease in the concentration of UA (by 22,3 %) in the 1st experimental group of rats to the level of 87,4±11,6 μmol/L, relative to the negative control (112,5±4,0 μmol/L), indicates a general pathology of the urinary systems induced by heavy metal. The revealed deviations in the indicators of the main biochemical markers of liver and kidney damage serve as a reliable argument characterizing cadmium as a pronounced hepato- and nephrotoxicant.

Introduction. This article presents the results of experimental simulation of the acute toxic effect of cadmium on the rat organism, its distribution in the liver, and kidneys. Activation of the protective mechanism against toxic metal through the metallothionein protein has to reduce the bioavailability of free cadmium. Material and methods. The study was conducted on rats weighing 140-190 g, which was once intragastrically injected with cadmium chloride in an amount of 1/20 LD50. We studied the time intervals: before intoxication, 1, 2, 4, 6, 24, 48, and 96 hours after inoculation. The accumulation of cadmium in the liver and kidneys was measured by atomic absorption spectrometry. The expression of the metallothionein gene (МТ1, МТ2А, МТ3) was determined using RT-PCR on RNA isolated from the same organs. Results. Quantitative differences in the metal content in the liver and kidneys are observed 1 hour after intoxication, with a cadmium content of 250 and 125 times higher than in the control groups, respectively. There is an accumulation of cadmium in the liver with a maximum after 6 hours, and then its redistribution to the kidneys. The pronounced expression of metallothionein with a single acute exposure to cadmium is tissue-specific, so the expression of the MT1 and MT2A genes was greatest in the liver and the MT3 gene in the kidneys. Discussion. After administration cadmium is mainly localized in hepatocytes and its concentration may exceed the ability of metallothionein to bind cadmium ions, which leads to histopathological changes in the liver. In response to the intake of metal in the cell, the expression pattern of many genes, including those associated with the activation of protective reactions, changes. Conclusion. Our data show a single exposure to cadmium to lead to an increase in the content of MT transcript in the liver and kidneys, simultaneously with the accumulation of metal in them. The nature of this accumulation depends on the organ, on the time of exposure, and gene expression also on the form of MT.

Introduction In modern conditions, caused by the pandemic of a new type of viral infection Covid 19, the use of paracetamol, which has hepatotoxic properties in overdose, has increased It seems relevant to study metabolic disorders in the liver in acute paracetamol intoxication and evaluate the effectiveness of the timely use of hepatoprotective drugs The purpose of this study is an experimental assessment of metabolic changes at the early stages of paracetamol exposure and pharmacological correction of toxic liver lesions with oxymethyluracil in comparison with known hepatoprotectors - ademetionine and Mexidol Material and methods Acute intragastric administration of paracetamol to laboratory animals was performed, and the corrective effect of the drug oxymethyluracil was studied in comparison with “Heptor” and “Mexidol” Biochemical studies of biomaterial of laboratory animals were conducted Results The analysis found the use of known hepatoprotectors and oxymethyluracil after exposure to paracetamol to normalize the biochemical parameters that characterize the functional state of the liver in laboratory animals Conclusion Oxymethyluracil, along with known hepatoprotectors, has a protective effect on the liver of laboratory animals under acute exposure to paracetamol comparable to, and in some cases exceeding, the corrective action of “Heptor” and “Mexidol” Введение В современных условиях, вызванных пандемией нового вида вирусной инфекции COVID-19, возросло применение парацетамола, обладающего гепатотоксическими свойствами при передозировке Представляется актуальным изучение метаболических нарушений в печени при острой интоксикации парацетамолом и оценка эффективности своевременного применения гепатопротективных препаратов Цель настоящего исследования - экспериментальная оценка метаболических изменений на ранних сроках воздействия парацетамола и фармакологическая коррекция токсических поражений печени оксиметилурацилом в сравнении с известными гепатопротекторами - «Гептором» и «Мексидолом» Материал и методы Проведено острое внутрижелудочное введение парацетамола лабораторным животным, изучено корректирующее действие препарата оксиметилурацила в сравнении с «Гептором» и «Мексидолом» Проведены биохимические исследования биоматериала лабораторных животных Результаты По результатам анализа установлено, что при применении известных гепатопротекторов и оксиметилурацила после воздействия парацетамолом происходит нормализация биохимических показателей, характеризующих функциональное состояние печени у лабораторных животных Заключение Оксиметилурацил наряду с известными гепатопротекторами оказывает защитное действие на печень лабораторных животных при остром воздействии парацетамолом, сопоставимое, а в некоторых случаях и превышающее корректирующее действие препаратов «Гептор» и «Мексидол»

Introduction. Cadmium is one of the most toxic heavy metals widely distributed in the environment. It has a long half-life, leading to its accumulation in various organs, which in turn is the cause of many adverse effects on human health. Material and methods. Acute toxic poisoning with cadmium chloride was simulated on white outbred male rats, divided into groups depending on the exposure time. Samples of liver and kidney tissues were used as study materials, in the homogenate of which the level of mRNA of metallothionein genes was determined. Results. It was found that the maximum value of the multiplicity of MT1 gene expression in the liver was reached after 6 hours (16.36 ± 0.77; p

Introduction. Among noninfectious diseases, one of the leading places belongs to pathologies caused by the action of industrial toxicants. In this regard, the search for drugs for the prevention and treatment of various intoxications is one of the priority tasks of public health. Treatment of intoxication with drugs with antioxidant and antihypoxic activity is more effective. The aim of this study was to investigate morphological changes in parenchymal organs (liver, kidneys, and pancreas) under acute exposure to high doses of carbon tetrachloride and to evaluate the effectiveness of their correction with a new composition of oxymethyluracil with ascorbic acid. Material and methods. The composition of 5-hydroxy-6-methyluracil with ascorbic acid was first synthesized at the Ufa Institute of Chemistry, Ufa Federal Research Center, RAS. The preventive effect of the new drug was studied in comparison with “Heptor” on the carbon tetrachloride-induced liver injury model. Morphological studies of the liver, pancreas, and kidneys of laboratory animals were carried out. Results. Studies have shown the prophylactic administration of new composition of 5-hydroxy-6-methyluracil with ascorbic acid to have a protective effect on the structure of parenchymal organs in acute carbon tetrachloride intoxication, comparable to the drug “Heptor” (possibly superior). However, reparative properties were observed only in the drug “Heptor”. Conclusion. Comparative estimation of morphological changes in parenchymal organs under acute exposure to high doses of carbon tetrachloride indicates the protective effect of prophylactic administration of the composition of 5-hydroxy-6-methyluracil with ascorbic acid, comparable to the drug “Heptor” (possibly superior).

Introduction. Toxic hepatitis (TH) is a complex and multifaceted disease, the development of which is mediated by a complex of biochemical and molecular genetic interactions. The current understanding of the pathogenesis of TH and, as a consequence, its treatment is based on standardization of the phenotype of the disease, often without taking into account metabolic disorders within the cells. Material and methods. experimental studies were performed on white outbred male rats weighing 200-220 g. A 50% solution of TCM was used as a toxicant. Biochemical studies were performed on a laboratory medical photometer “Stat Fax 3300” using clinical test kits and control materials manufactured by Vector-Best LLC. Liver tissue for histological examination was subjected to the standard histological procedure and paraffin embedding. Sections 5-7 μm thick were stained with hematoxylin-eosin. Gene expression analysis was performed using real-time PCR amplification on a RotorGene instrument (QIAGEN). Statistical processing of experimental data was performed using the Pearson correlation coefficient and one-way analysis of variance (ANOVA). The results were considered reliable at p

Introduction. The high frequency of chemical poisoning is accompanied by an increase in the absolute number of cases of chemical damage to the liver. There is growing evidence that acute chemical poisoning in Russia is among the leading non-infectious diseases leading to premature death of male and female working-age people. It seems relevant to search for new pharmacological agents with low toxicity and high hepatoprotective activity, which increase the body’s stability under the influence of adverse environmental factors. The use of metabolic action drugs combining antioxidant and antihypoxic activity as hepatoprotectors is promising. The purpose of this study is an experimental evaluation of the hepatoprotective activity of a new composition of oxymethyluracil with succinic and fumaric acids. Material and methods. The composition of 5-hydroxy-6-methyluracil with succinic and fumaric acids was first synthesized at the Ufa Institute of Chemistry. Using the model of acute liver toxic damage with carbon tetrachloride in laboratory animals, the prophylactic effect of a new drug was studied in comparison with heptor (ademetionine). Biochemical and morphological studies of laboratory animals’ biomaterial were conducted. Results. The analysis showed that when using the studied drugs, biochemical parameters were close to the level of control animals. Morphological changes in the liver were less pronounced in the group of animals treated with the new composition, compared with changes in the structure of the liver of animals treated with heptorator (ademetionin). Conclusion. The new composition of 5-hydroxy-6-methyluracil with succinic and fumaric acids has a protective effect on the liver of laboratory animals with the acute toxic effects of carbon tetrachloride, comparable, and in some cases, exceeding the preventive effect of heptoperam (ademetionine).

Sudden anosmia and/or ageusia is one of the first and significant symptoms of COVID-19, which are manifested in good health and a successful course of the disease. Purpose: to analyze neurological disorders in COVID-19 and present the results of peripheral neuropathy of the olfactory nerve. We present the results of 39 (32 %) patients with olfactory dysfunction obtained among 121 patients with a positive RT-PCR test for COVID-19. The data was collected through a sur-vey and questionnaire based on the AAO-HNS anosmia reporting tool. The majority of individuals (32 patients) did not have close contact with a positive case in the recent past. Most patients regained their sense of smell within 1-2 weeks of the onset of anosmia. To date, the mechanisms of anosmia in SARS-CoV-2 are not yet clear. It remains debatable whether anosmias are the result of nerve damage or inflammation of the olfactory nerves, which requires further research. Key words: anosmia, loss of smell, dysgeusia, neuroinflammation, olfactory dysfunction, SARS-COV-2, COVID-19.

Introduction: WAG/Rij rat is an experimental model of retinal degenerative diseases intensifying with age. Degeneration begins in the photoreceptor cells layer, followed by disappearance of photoreceptor cells, migration of the pigment epithelium and disorganization of remaining retinal layers. However, the age of onset of the degeneration is unknown. The destroyed neurons of retina are usually replaced by glial cells. A typical marker for several types of glial cells is the glial fibrillary acidic protein (GFAP).Aim of the Work: The aim of the study is to determine postnatal changes of GFAP expression in retina of WAG/Rij rats.Material and Methods: WAG/Rij rats of both sexes and different ages: 1, 10, 15, 20, 30, 60, 180, 360 postnatal days (P) (n =3 for each age) were taken. The immunohistochemical analysis of GFAP expression in the retina of WAG/Rij rats was performed and the expression area was measured.Results: Expression of GFAP in the retina is detected from P1 to P20 as a brown staining in the internal limiting membrane or as a brown lines on the inner retina. On P30 the glial fibrillary acidic protein is already detected in significant quantities in almost all layers of the retina of the experimental rats. From P60 to P360 the expression of GFAP in the retina of the WAG/Rij rats is more pronounced and increases in direct proportion with the age.Conclusion: It was found that GFAP expression in the retina of WAG/Rij rats increases in direct proportion to the age. The increasing GFAP expression in the retina of the WAG/Rij rats starting from the 30th postnatal day indicates an intensification of destructive processes in retinal neurons with age and their replacement by Muller cells.

Absorbed dose to water was measured with ionisation chambers NE 2561 (#267), NE 2581 (#334), NE 2571 (#1028), using the IAEA standard water phantom. The ionisation chamber was inserted in the water phantom at a reference depth dependent on the type of the radiation quality used. Three radiation qualities were used namely 1.25 MeV gamma ray, 6 MV x-rays and 10 MV x-rays. The values of the absorbed dose to water were determined by the N(K)- and N(X)- based methods, i.e with the use of IAEA, HPA, NACP, AAPM, NCRP and ICRU protocols. The aim of this study was to make an intercomparison of the results, by taking the IAEA protocol as a standard. The largest deviation contributed by any of these protocols was recorded for each quality. It was found that AAPM, NCRP and ICRU protocols contributed 0.94% for 1.25 MeV gamma ray, NACP contributed 2.12% for the 6 MV x-rays, and NACP contributed 2.35% for 10 MV x-rays. Since the acceptable limit of deviation set by the IAEA for this absorbed dose work is ± 3%, it is clear that the overall deviations obtained were all satisfactory.

A constitutive model that couples elastic-plastic and damage theories is developed to predict the mechanical behavior of a shale from the Mont Terri rock laboratory (Opalinus Clay). The framework of continuum damage mechanics allows to predict the degradation of the elastic parameters with strains, while the coupling with plasticity correctly reproduces the irreversible strains typical of hard clayey materials. The yield surfaces (one for damage and one for plasticity) are postulated and the evolution equations of the internal variables are derived throughout the application of normality rule. Thermodynamic consistency of the model is investigated. The plastic behavior is described with a non-linear strain hardening function and is coupled with an isotropic damage model suitable for brittle and quasi-brittle geomaterials. The model is integrated with an implicit scheme that guarantees convergence and accuracy. Numerical simulations carried out with the proposed model in triaxial conditions well reproduced observed behavior from experiments.