Gulnaz Gabidinova
@kazangmu.ru
Department of Hygiene and Occupational Medicine
Kazan State Medical University
RESEARCH, TEACHING, or OTHER INTERESTS
Toxicology, Health, Toxicology and Mutagenesis, Molecular Biology
Scopus Publications
Scopus Publications
Liliya M. Fatkhutdinova, Gulnaz F. Gabidinova, Amina G. Daminova, Ayrat M. Dimiev, Timur L. Khamidullin, Elena V. Valeeva, Agboigba Esperant Elvis Cokou, Shamil Z. Validov, and Gyuzel A. Timerbulatova
Elsevier BV
Liliya M. Fatkhutdinova, Gulnaz F. Gabidinova, Аirat М. Dimiev, Elena V. Valeeva, and Gyuzel A. Timerbulatova
Federal Scientific Center for Hygiene F.F.Erisman
Introduction. Carbon nanotubes (CNTs) are a group of promising nanomaterials for industrial and biomedical applications. There has been shown influence of the physicochemical characteristics of CNTs on the toxic effects, including the ability to cause DNA damage and induce apoptosis. In this study, there was carried out a comparative assessment of pro-apoptotic effects under exposure to single-walled and multi-walled CNTs produced in Russia on human respiratory cells.
 Materials and methods. Human bronchial epithelial cells BEAS-2B, alveolar epithelial cells A549, and lung fibroblasts MRC5-SV40 were exposed to pristine and purified TUBALLTM SWCNTs and Taunit-M MWCNTs. In cells exposed to 4 concentrations (100, 50, 0.03, 0.0006 μg/ml) of all types of CNTs for 72 hours, the level of mRNA of the P53, BAX and BCL2 genes, as well as the level of reactive oxygen species were assessed.
 Results. All types of CNTs initiated apoptosis in human respiratory epithelial cells BEAS-2B and A549, but not in MRC5-SV40 lung fibroblasts. BEAS-2B were more sensitive to the effects of MWCNTs, while A549 were more sensitive to pristine SWCNTs. Apoptosis was initiated at low concentrations, including those corresponding to industrial exposures. The mechanism of oxidative stress could act as a factor in triggering apoptosis in lung epithelial cells.
 Limitations. Relatively short (72 hours) cell incubation time and the use of 2D cell models that do not consider real cell interactions.
 Conclusion. There were revealed differences in the mechanisms of initiation of the internal pathway of apoptosis and sensitivity to different types of CNTs depending on the type of epithelial cells. Comparative analysis of the initiation of apoptosis by different types of CNTs has shown that there are differences in potential target cells and toxic mechanisms, which should be considered in further studies.
Liliya M. Fatkhutdinova, Olesya V. Skorokhodkina, Laila I. Yapparova, Milyausha R. Khakimova, Alfrit R. Rakhimzyanov, Anastasiya V. Ablyaeva, Aleksei I. Noskov, Gulnaz F. Gabidinova, Gyuzel A. Timerbulatova, and Ramil R. Zalyalov
Federal Scientific Center for Hygiene F.F.Erisman
The aim of the study was to investigate the effect of fine suspended particles in the atmospheric air on the formation and course of allergic and non-allergic phenotypes of the T2 endotype of bronchial asthma (BA) using the case-control study. Materials and methods. BA patients were selected in the course of seeking medical help. The groups were formed on the base of matching criteria (gender, age, body mass index, level of education), supplemented by the collection of information about potential cofounders. Based on the data on monitoring the content of fine suspended particles in the atmospheric air of Kazan, the average annual and maximum concentrations of PM2.5 and PM10 fractions were determined in the residential areas. The group of “cases” included forty patients with an allergic phenotype and 42 patients with an eosinophilic non-allergic phenotype of bronchial asthma, the control group included forty eight people. Additionally, sampling of atmospheric air was carried out using an 8-stage impactor to assess the content of bacterial endotoxin, and elemental composition. Results. Higher levels of pollution with fine suspended particles were demonstrated in the areas of residence of BA patients, comparing to the control group. An increase in the average annual concentration of the PM2.5 by 10 µg/m3 increases the odds of the eosinophilic non-allergic BA phenotype in adults by 4.76 times. The odds of the allergic phenotype of bronchial asthma increases in the presence of bacterial endotoxin - 1.32 times per 0.01 EU/m3 of endotoxin in the 3.2-18 µm size fraction. A more severe course of the eosinophilic non-allergic BA phenotype was noted at higher average annual concentrations of the PM2.5. The control of allergic asthma depends on the bacterial contamination of the aerosol. Limitations of the study are related to the use of geospatial approach to assess personalized average annual and maximum annual concentrations. Conclusion. The role of fine suspended particles in the atmospheric air in the development of bronchial asthma in adults has been shown. Various mechanisms were established to be involved in the formation of the clinical picture of the eosinophilic non-allergic and allergic phenotypes of bronchial asthma.
G. F. Gabidinova, G. A. Timerbulatova, A. G. Daminova, Sh. F. Galyaltdinov, A. M. Dimiev, M. A. Kryuchkova, R. F. Fakhrullin, and L. M. Fatkhutdinova
Federal Scientific Center for Hygiene F.F.Erisman
Introduction. In the present study, a comparative assessment of the toxic effects of industrial single-walled and multi-walled carbon nanotubes (SWCNT and MWCNT) at doses corresponding to industrial exposures on BEAS-2B and A549 cells was carried out. Materials and methods. The size distribution of SWCNT and MWCNT agglomerates in dispersions was estimated by dynamic light scattering and transmission electron microscopy. Cytotoxicity was assessed using a MTS test and LDH assay. The interaction of CNTs with cells was visualized using dark-field and transmission electron microscopy. Results. Cytotoxic effects of pristine SWCNT and MWCNT in concentrations of 50-200 μg/ml and purified SWCNT in the range of 25-200 μg/ml were found in BEAS-2B cells. SWCNT and MWCNT were found to penetrate into the cytoplasm of both BEAS-2B and A549 cells, while MWCNT are more often revealed in the intracellular content as vacuolized clusters, and single SWCNT and agglomerates are visualized in the cytoplasm without a tendency to vacuolization. Limitations. CNT were introduced into cells in the form of dispersions, where both single nanotubes and their agglomerates were found. The calculation of CNT concentrations for introduction into cells was based on computer simulation. Conclusion. Further study of the mechanisms of cytotoxic and genotoxic effects of different types of carbon nanotubes (CNT) may contribute to the identification of MWCNT and SWCNT specific effects on the cells of the respiratory system to develop methodological approaches to the safe use of CNT.
F. V. Valeeva, M. S. Medvedeva, T. A. Kiseleva, K. B. Khasanova, and G. F. Gabidinova
Endocrinology Research Centre
BACKGROUND: Depending on the polymorphism of genes that that are involved in metabolism, the response of patients to different types of therapy may differ. Despite the potential effect of rs7903146 TCF7L2 and rs1042712 ADRB2 on changes in body composition in different types of therapy of early carbohydrate metabolism disorders, these associations haven’t been studied yet. AIM: To study the influence of rs7903146 TCF7L2, rs1042714 ADRB2 on changes in body fat composition in different types of therapy of early carbohydrate metabolism disorders.MATERIALS AND METHODS: The study involved patients with overweight or obesity and risk factors for Type 2 Diabetes development. All patients underwent genotyping with the real-time polymerase chain reaction, oral glucose tolerance test and bioimpedancemetry. Further, the patients were divided into two groups. First group kept a diet with the exclusion of simple and limitation of complex carbohydrates and fats. Second group took metformin in addition to the diet. Three months after bioimpedancemetry was performed again.RESULTS: The research involved 73 patients (the mean age 48±12 y.o., the mean BMI 34,27±6,18 kg/m2 ). The diet therapy group consisted of 47 people. Other 26 patients took metformin in addition to the diet. In group of diet, T allele carriers of rs7903146 TCF7L2 were characterized with more decrease in fat mass compared with CC homozygotes (- 7.90 ± 9.46% vs. -1.54 ± 8.98%, p = 0.027). CC genotype carriers of rs7903146 TCF7L2 in group of metformin and the diet had a tendency for more decrease in hip circumference compared with T allele carriers (-4.95 ± 3.34% vs. — 2.5 ± 2.96%, p = 0.064). Carriers of C allele in homozygous state of rs1042714 ADRB2, who took metformin with the diet, demonstrated more decrease in hip circumference (- 5.81 ± 3.00% vs. -2.50 ± 2.7%, p = 0.009), the tendency for decrease in fat mass (-8.28 ± 8.86% vs. — 3.20 ± 5.09%, p = 0.068) and waist circumference (-5.91 ± 4.29% vs. -3.03 ± 4.01 %, p = 0.091) compared with G allele carriers. The association of rs7903146 TCF7L2 and rs1042714 ADRB2 with changes in total body weight was not observed (p> 0.05).CONCLUSION: Single nucleotide polymorphisms rs7903146 TCF7L2 and rs1042714 ADRB2 influence on body fat composition in patients with early carbohydrate metabolism disorders in various types of treatment.
G A Timerbulatova, P D Dunaev, A M Dimiev, G F Gabidinova, N N Khaertdinov, R F Fakhrullin, S V Boichuk, and L M Fatkhutdinova
ECO-Vector LLC
Aim. Comparative assessment of the effect of fibrous materials on cell cultures RAW264.7 and BEAS-2B.
 Methods. The effects of various fibrous materials single-walled carbon nanotubes of two types (SWCNT-1 and SWCNT-2), differing in morphological characteristics, and chrysotile asbestos as a positive control was assessed on two cell lines macrophages RAW 264.7 and human bronchial epithelium BEAS-2B cells. The studied materials concentration range for experiments on cells was selected taking into account the SWCNT content in the air of the working area and the subsequent modeling of SWCNT deposition in the human respiratory tract. Suspensions of the studied materials were prepared based on cell culture media by ultrasonication. Cytotoxicity assessment after 48 hours of incubation was performed by using the MTS colorimetric assay. The expression level of apoptosis markers was assessed by immunoblotting using the corresponding monoclonal antibodies. Visualization of SWCNT-1, SWCNT-2 and chrysotile asbestos in BEAS-2B cell cultures was carried out by improved dark-field microscopy.
 Results. According to dark-field microscopy, all the studied fibrous materials were found on the surface or cytoplasm of the cells. SWCNT and chrysotile asbestos did not have a direct cytotoxic effect in the MTS assay and did not induce apoptosis according to the results of Western blotting in cell cultures of RAW264.7 macrophages and BEAS-2B bronchial epithelium. In the cells of the bronchial epithelium (BEAS-2B) that showed greater sensitivity, a slight increase in the expression of pro-apoptotic protein PARP, which was more pronounced for shorter SWCNT-2, was revealed.
 Conclusion. Both types of SWCNTs, despite the differences in morphological characteristics, demonstrated similar effects in in vitro experiments; this result, with its further verification, can have an important practical application in justifying approaches to determining the safety criteria for single-walled carbon nanotubes as a class of nanomaterials of the same type.
Liliya M. Fatkhutdinova, Gulnara G. Badamshina, Elena P. Sizova, Marina A. Patyashina, Lidiya V. Stavropolskaya, Gulnaz F. Gabidinova, and Ramil R. Zalyalov
FSBI Research Institute of Occupational Health RAMS
Introduction. To date, issues related to the protection of medical workers from COVID-19 infection, including immunological protection, are of particular interest. The aim of the study was to explore seroprevalence of the IgG to SARS-CoV-2 N-protein in various groups of medical workers with the following assessment of the risk of COVID-19, depending on the seropositivity and occupational group. Materials and methods. The study of the strength of immunity to COVID-19 was carried out within the framework of the large-scale Rospotrebnadzor program to assess population immunity to the SARS-CoV-2 virus in the population of the Russian Federation, considering the protocol recommended by WHO, on the basis of the laboratories of the Center for Hygiene and Epidemiology in the Republic of Tatarstan. From the sample of the study conducted in the Republic of Tatarstan, medical workers (301) were selected without a history of a new coronavirus infection and with no clinical symptoms of this disease at the time of biomaterial sampling (June 2020); the absence of the transferred new coronavirus infection was verified by the Unified State Information System "Electronic Health of the Republic of Tatarstan". The comparison group included 52 employees belonging to the engineering and technical personnel and not employed in medical institutions who met the above inclusion criteria. In the aggregate, the observation group (medical workers and the comparison group) included 12.1% of the participants in the population study. Results. The rate of seropositivity was 36.5% in the control groups, 23.7% - in doctors, and 38.9% - in nurses. Compared to doctors, seroprevalence was higher in nurses. The employment of medical workers in temporary infectious diseases hospitals did not affect the production of the IgG to SARS-CoV-2 N-protein. A relatively low prevalence of seropositivity among doctors of temporary infectious diseases hospitals was revealed. The probability of seroconversion decreased with age and did not depend on gender or history of recent contacts with COVID-19 patients. The survival analysis showed that the probability of remaining healthy by the end of the follow-up was the lowest among doctors from medical and preventive institutions that did not serve as temporary infectious diseases hospitals. The risk of COVID-19 in seronegative individuals was higher, but without statistical significance. Conclusion. According to the data of immunological studies for the presence of IgG antibodies to the nucleocapsid protein of the SARS-CoV-2 virus, it was found that the prevalence of seroprevalence in nurses is significantly higher than that of doctors, nurses of medical and prophylactic organizations of young age have higher seroprevalence to the nucleocapsid protein of the SARS-CoV-2. According to prospective observation, it was revealed that doctors of medical and prophylactic organizations that are not classified as temporary infectious diseases hospitals have a higher risk of developing a symptomatic form of COVID-19, which may be due to both the insufficient effectiveness of anti-epidemic measures and the peculiarities of the immune response and approaches, used to evaluate it. In the current epidemic situation, the detection of IgG antibodies to the SARS-CoV-2 virus can be used to decide on the distribution of responsibilities among medical personnel.
A. A. Antsiferova, G. A. Timerbulatova, G. F. Gabidinova, D. O. Nikitin, A. M. Dimiev, Sh. F. Galyaltdinov, A. V. Vershinin, P. K. Kashkarov, and L. M. Fatkhutdinova
Pleiades Publishing Ltd
Milyausha R. Khakimova and Gulnaz F. Gabidinova
FSBI Research Institute of Occupational Health RAMS
Introduction. Suspended particles in ambient air of cities increase the risk of developing respiratory and cardiovascular diseases. At the same time, data on the role of suspended particles in the formation and complication of the course of bronchial asthma (BA) are extremely limited. The aim of study was to substantiate the design of a study to study the effect of fine suspended particles in atmospheric air on the development of the T2 endotype of BA. The design of a "case-control" study was developed and implemented, including patients with the T2-endotype of BA and persons in the control group. In order to verify the diagnosis of BA, General clinical methods of examination and specific allergological examination are used. In parallel, the quantitative characteristics and qualitative composition of suspended particles in atmospheric air are studied with the determination of the mass of suspended particles, dispersion, chemical and microbiological (muldi-tof mass spectrometry, PCR analysis) composition. Atmospheric air samples will be collected using a cascade impactor in the area where patients with bronchial asthma and control groups live. For each fraction, the following will be analyzed: suspended particle mass, dispersion, chemical and microbiological (muldi-tof mass spectrometry, PCR analysis) composition. Conclusions. The study will assess the risk of T2-endotype formation of bronchial asthma with various quantitative and qualitative characteristics of suspended microparticles in the atmospheric air.
Gulnaz F. Gabidinova
FSBI Research Institute of Occupational Health RAMS
Introduction. Due to the expansion of production volumes and applications of multi-wall carbon nanotubes (MWCN), a comprehensive toxicological assessment of the nanomaterial is required, followed by the development of approaches to regulating their content in various facilities to reduce the risks of adverse effects on human health. The aim of the study was to assess the state of the nervous system of experimental animals in response to intrapharyngeal introduction of MWCN in doses corresponding to real production exposures. Materials and methods. The object of the study was two-month-old C57BL mice. The experimental groups received by pharyngeal aspiration 20 mcg of MWCN in 0.1% solution of Twin 80; the control group was administered 0.1% Twin 80 in the same way. The nervous system was evaluated 24 hours and 30 days after exposure in a battery of behavioral tests. Results. The use of the "Open field" method allowed us to establish signs of increased anxiety and weakening of research responses in the experimental group 24 hours after exposure. After 30 days, the experimental group showed an increased level of anxiety in variable stress conditions compared to the control group. Conclusions. Thus, the conducted studies revealed some behavioral deviations in the experimental group compared to the control group 24 hours and 30 days after exposure, which suggests the presence of a General systemic or stress reaction to the introduction of the MWCN suspension.