Samat S. Baygildin

Ufa Research Institute of Occupational Health and Human Ecology

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ДО

Д О Каримов

Ufa Research Institute of Occupational Health and Human Ecology

ЕF

Е. F. Repina

Ufa Research Institute of Occupational Health and Human Ecology

Nadezhda Yu. Khusnutdinova

Ufa Research Institute of Occupational Health and Human Ecology

Denis A. Smolyankin

Ufa Research Institute of Occupational Health and Human Ecology

ГВ

Г В Тимашева

Ufa Research Institute of Occupational Health and Human Ecology

АР

А. Р. Гимадиева

Ufa Institute of Chemistry

АБ

А Б Бакиров

Bashkir State Medical University

Yana V. Valova

Ufa Research Institute of Occupational Health and Human Ecology

ЭР

Э Р Шайхлисламова

Ufa Research Institute of Occupational Health and Human Ecology

ЛА

Л. А. Мусина

Bashkir State Medical University

Cooperative Institutions

Ufa Research Institute of Occupational Health and Human Ecology

Bashkir State Medical University

Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Bashkir State University

University of Science and Technology

Russian Academy of Sciences

Ministry of Health of the Russian Federation

Academy of Sciences of the Republic of Bashkortostan

Ufa Institute of Chemistry

Korea University of Science and Technology

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Conflict of interest: the authors declare no conflict of interest.

Journal Biomed (2021)

Samat S. Baygildin Л. А. Мусина З. Р. Хисматуллина

Retinal degenerations comprise a large heterogeneous class of diseases (dystrophies) of retina leading to a progressive vision loss. The emergence of new experimental therapies (gene and cell therapy, regenerative ophthalmic surgery) generates a demand for new experimental models. The review tackles various animal models of human retinal degenerative diseases. Pros and contras of induced and genetic experimental models are highlighted. An adequate experimental model choice may condition a pathogenetic approach to retinal disease therapy.

10.33647/2074-5982-17-1-70-81

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Experimental assessment of the protective effect of hydroxymethyluracil complex compounds under extreme exposure to acrylamide

Hygiene and Sanitation (2023)

Nadezhda Yu. Khusnutdinova Е. F. Repina T. G. Yаkupova А. Р. Гимадиева Д О Каримов

Introduction. Acrylamide is widely used in industry. Considering the potential danger of acute acrylamide poisoning, it seems urgent to search for new effective ways to protect and increase the body’s resistance to extreme exposure. The purpose of the study is to conduct a comparative assessment of the protective effect of hydroxymethyluracil complex compounds when administering moderate lethal doses of acrylamide to laboratory animals. Materials and methods. The subacute experiment was conducted on thirty outbred male rats weighted of 189–194 g. For 14 days, a toxicant was administered intragastrically at a dose of 20 mg per kg of body weight, then a single dose of 200 mg per kg of body weight was administered. Animals received complex compounds of hydroxymethyluracil with ascorbic acid and sodium succinate (50 mg per kg body weight), with acetylcysteine (500 mg per kg body weight) one hour before acrylamide. Against the background of the administration of complex compounds without acrylamide to the animals. Then one week later, an analysis of the mortality was carried out, and the weight coefficients of the liver and kidneys were determined in the surviving animals. Results. When acrylamide was administered to animals at the level of average lethal doses, 4 out of 6 animals died in the positive control group. In the groups in which animals received, in addition to acrylamide, the compound of hydroxymethyluracil with ascorbic acid and sodium succinate, the death rate was 2 out of 6 rats. Among the animals that received the compound of hydroxymethyluracil with acetylcysteine, no mortality was recorded within 7 days, as in the group negative control. Limitations of the study are that the protective effect of hydroxymethyluracil complex compounds was assessed only on one species and gender of laboratory animals. Conclusion. The complex compound of hydroxymethyluracil with acetylcysteine has a significant protective effect on male rats under extreme exposure to acrylamide at the level of moderate lethal doses. For a more complete understanding of the mechanism of action and a final judgment about the protective properties of the being studied complex compounds, it is necessary to continue research with analysis of changes in other indicators of the health status of laboratory animals.

Toxicant

10.47470/0016-9900-2023-102-11-1236-1240

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Evaluation of apoptosis gene expression and morphological changes in kidney tissue under acrylamide exposure and prophylactic drug correction

Hygiene and Sanitation (2025)

Е. F. Repina Д О Каримов Samat S. Baygildin Татьяна Георгиевна Якупова Nadezhda Yu. Khusnutdinova

Introduction. Acrylamide is a well-known toxicant, contact with which occurs both in industrial and domestic conditions. It has been found to have nephrotoxic properties. The purpose of the work is to evaluate the expression of the Casp7, Chek1 genes and changes in the structure of the kidney tissue in rats under long-term exposure to acrylamide and preventive correction. Materials and methods. The experiment used sixty white outbred male rats. Acrylamide was administered intragastrically at a dose of 5 mg/kg body weight for 90 days. Correction of possible violations was carried out 1 hour before the administration of the toxicant with complex compounds of hydroxymethyluracil. Gene expression was studied using real-time PCR. SPSS Statistics 21.0 software (IBM, USA) was used for statistical data analysis. Morphological studies of the structure of rat kidneys were carried out using standard methods. Results. Studies have shown that exposure to acrylamide for 3 months at a dose of 5 mg/kg body weight causes structural changes in the kidney tissue in rats. With long-term exposure to acrylamide, there is a tendency to increase the expression of the Chek1 and Casp7 genes, which may indicate cell damage and activation of repair and apoptosis processes in them. The combination of hydroxymethyluracil with acetylcysteine had the greatest protective effect on the structure of the kidneys and the expression of the Casp7 gene. Limitations are that morphological changes in kidney tissue during long-term exposure to acrylamide were correlated with the expression of only two apoptotic genes. For a more complete understanding of the pathogenetic changes during the damaging effect of acrylamide on the kidneys, it is necessary to conduct a multivariate analysis taking into account other toxicological and genetic indicators. Conclusion. Acrylamide, when ingested for a long time at a dose of 5 mg/kg body weight, has a nephrotoxic effect, which is confirmed by data from morphological studies and a tendency to increase the expression of the main apoptosis genes in kidney tissue. The best protective effect according to the studied parameters was observed with the prophylactic administration of a complex compound of hydroxymethyluracil with acetylcysteine.

10.47470/0016-9900-2025-104-1-96-100

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Features of metabolic changes in the liver in experimental animals under chronic exposure to acrylamide and against the background of its preventive correction

Hygiene and Sanitation (2023)

Е. F. Repina T. G. Yаkupova Д О Каримов Г В Тимашева Э Р Шайхлисламова

Introduction. Acrylamide used industrially is also widely known to be a toxic compound produced during high temperature cooking. Given the danger of its entry into the body, it is important to continue fundamental research to study the mechanism of its toxicity and search for effective ways to correct the disorders caused by it. The purpose of the research is to study the features of metabolic changes in the liver of rats under conditions of chronic exposure to acrylamide and evaluate the effectiveness of their preventive correction with oxymethyluracil complex compounds. Materials and methods. Studies were performed on sixty white outbred male rats weighing 180–200 g. Acrylamide was administered intragastrically at a dose of 5 mg/kg of body weight for 90 days. Correction of possible disorders was carried out 1 hour before the administration of the toxicant with complex compounds of oxymethyluracil with ascorbic acid (MG-1), with sodium succinate (MG-2) and acetylcysteine (MG-10). Biochemical parameters were studied after 45 and 90 days of the experiment. Results. Studies have shown long-term intake of acrylamide at a dose of 5 mg/kg of body weight to lead to metabolic disorders. A statistically significant increase in the activity of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and superoxide dismutase (SOD) was found. Statistically significant differences in the level of activity of ALT, alkaline phosphatase and SOD for the period of the experiment of 45 days compared with the positive control group were established in the group receiving the MG-10 preparation. After 90 days, in the group of animals treated with the MG-2 preparation, the activity of ALT and alkaline phosphatase decreased significantly. The introduction of the drug MG-10 had a statistically significant effect on ALT activity, reducing it to the level in the negative control group of animals treated with distilled water. Limitations of the study are related to the correction with complex compounds of oxymethyluracil carried out only in a prophylactic regimen. For the final judgment on their protective effectiveness, it is necessary to introduce them in the accompanying and restorative regimes, as well as to study other biochemical parameters when exposed to acrylamide. Conclusion. The best protective effect at a period of 45 days was shown by a complex compound of oxymethyluracil with acetylcysteine, at a period of 90 days – a complex compound of oxymethyluracil with sodium succinate.

Toxicant

10.47470/0016-9900-2023-102-9-975-980

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EXPERIMENTAL EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF A NEW COMPOSITION OF OXIMETHURACIL WITH CARBONIC ACIDS

Hygiene and Sanitation (2019)

Е. F. Repina Д О Каримов Г В Тимашева Nadezhda Yu. Khusnutdinova А. Р. Гимадиева

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).

Fumaric acid

Succinic acid

10.18821/0016-9900-2019-98-9-1004-1010

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Cadmium distribution and metallothionein expression in rat organs following acute intoxication

Hygiene and Sanitation (2020)

Anna S. Fazlieva Elza N. Usmanova Р А Даукаев Д О Каримов Yana V. Valova

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.

Metallothionein

Cadmium chloride

CADMIUM EXPOSURE

10.47470/0016-9900-2020-99-9-1011-1015

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Glial fibrillary acidic protein expression in postnatal development of WAG/Rij rat retina

The Egyptian Journal of Histology (2020)

Л. А. Мусина Samat S. Baygildin Зухра Хисматуллина

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 Müller cells.

Inner limiting membrane

GFAP stain

Neuroglia

10.21608/ejh.2020.24728.1255

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Evaluation of the potentiating effect of polystyrene microparticles on the toxicity of acrylamide and ethanol under conditions of combined treatment of mouse hepatocyte cell culture MH-22a

Hygiene and Sanitation (2024)

Eldar R. Kudoyarov Д О Каримов Alina A. Gizatullina Denis D. Karimov Samat S. Baygildin

Introduction. Microparticles of polymer compounds are common in the environment. polystyrene particles are the most common types of microplastics. The most interesting subject of the study is the assessment of the potentiating properties of microplastics on the manifestations of toxicity of common substances entering the body by alimentary means, primarily such as acrylamide and ethanol. Materials and methods. The experimental work was performed on a cell culture of mouse MH-22a hepatocytes in compliance with the principles of working with mammalian cell cultures. An MTT test was used to study cell viability by respiratory activity. The statistical analysis was performed in the SPSS Statistics 21 software. Results. The article presents the results of an experimental study of the respiratory activity of cells under combined treatment with 300 nm polystyrene microparticles at a concentration of 0.025% with acrylamide and ethanol. Preliminary experimental data is presented to substantiate the selected concentration of the microplastic under study, demonstrating its low acute cytotoxicity. The calculated IC50 values for cell survival for acrylamide and ethanol under single exposure and combined exposure with polystyrene microparticles for 24 hours had insignificant differences. Limitations. The study was performed on a cell culture of mouse MH-22a hepatocytes (monolayer) cultured in accordance with the requirements of the culture passport and treated with 300 nm polystyrene microparticles and their mixtures with acrylamide and ethanol only for 24 hours in microplate format. Conclusion. A comparative analysis of survival values when exposed to toxic substances without addition and in the presence of microplastics revealed no significant differences between cell groups, which at the moment did not allow detecting the potentiating effect of polystyrene microparticles with a size of 300 nm on the toxicity of acrylamide and ethanol under 24-hour combined treatment.

10.47470/0016-9900-2024-103-7-737-743

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Metabolic changes on the background of acute exposure to paracetamol and evaluation of the effectiveness of hepatoprotective drug

Hygiene and Sanitation (2020)

Г В Тимашева Д О Каримов Е. F. Repina Denis A. Smolyankin Nadezhda Yu. Khusnutdinova

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”.

Acetaminophen

10.47470/0016-9900-2020-99-9-1016-1021

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ASSESSMENT OF MT1A AND MT2A GENE EXPRESSION IN THE LIVER OF RATS DURING ALUMINUM HYDROXIDE INTOXICATION

SCIENTIFIC MEDICAL BULLETIN OF UGRA (2024)

Yana Valerievna Valova Alina A. Gizatullina D.A. Smolyankin Samat S. Baygildin Eldar R. Kudoyarov

Aluminum is one of the most widely used metals in a variety of industries, including the food and pharmaceutical industries, resulting in the human body being exposed to significant amounts of metal and/or its compounds on a daily basis. The purpose of the study was to evaluate the expression of the Mt1a and Mt2a genes in the liver of rats during intoxication with various doses of aluminum hydroxide in a subacute experimental model. Expression in kidney tissue was assessed by real-time PCR. As a result of the experiment, it was shown that oral administration of aluminum hydroxide at a dose of 0.15 mg/kg for 1 month led to a decrease in the level of expression of the MT1A and MT2A genes in the liver of experimental rats

10.25017/2306-1367-2024-40-37-42

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