Pub Date : 2023-02-28DOI: 10.47470/0869-7922-2023-31-1-4-17
Y. S. Goldfarb, A. N. Yelkov, A. V. Badalyan, Mikhail Mikhailovich Potshveriya, E. E. Bitkova
The aim of the study. Obtaining new data on the pathogenesis of endotoxicosis (ET) in the rehabilitation period of acute poisoning by assessing the conjugacy of hemorheology (HR) disorders with the development of ET. Material and methods. To obtain new information about the pathogenesis of acute poisoning in the rehabilitation period in 145 patients with severe acute poisoning with psychopharmacological agents (PFAp) due to the addition of pneumonia, neurotoxicants (NTp) with the development of toxic hypoxic encephalopathy and corrosive substances (CSp) with deep and widespread burns of the mucous membranes of the gastrointestinal tract, a pair correlation analysis of the block structure of the obtained correlation matrix was undertaken, establishing the relationship between the two indicators, as well as a canonical correlation analysis revealing the nature of the statistical relationship between groups of indicators, with the calculation of the canonical correlation coefficient. Results. As a result, statistically significant correlations were established between the indicators HR (viscometric, aggregation and indicators hemostasis) and ET (total and effective albumin concentration, the level of medium molecular weight peptides, the content of leukocytes, lymphocytes, neutrophils and circulating immune complexes detected in the blood, and his integral indicators) (-0.32-0.48 for PFAp, 0.29-0.35 for NTp and 0.28-(-0.51) for CSp), as well as statistically significant values canonical correlation coefficients, which indicated the development of ET due to disorders of HR. Limitations. The study was performed on laboratory data obtained during the examination of patients with acute poisoning, and therefore has no restrictions for the further use of this methodological approach in clinical trials. Conclusion. The obtained data can serve to optimize the treatment of ET in this pathology by targeted therapeutic effects on parameters of HR (on viscosity and hemostasis in PFAp and NTp, and in CSp, in addition, on aggregation).
{"title":"The relationship of hemorheological disorders with the development of endotoxicosis in the rehabilitation period of acute poisoning","authors":"Y. S. Goldfarb, A. N. Yelkov, A. V. Badalyan, Mikhail Mikhailovich Potshveriya, E. E. Bitkova","doi":"10.47470/0869-7922-2023-31-1-4-17","DOIUrl":"https://doi.org/10.47470/0869-7922-2023-31-1-4-17","url":null,"abstract":"The aim of the study. Obtaining new data on the pathogenesis of endotoxicosis (ET) in the rehabilitation period of acute poisoning by assessing the conjugacy of hemorheology (HR) disorders with the development of ET. Material and methods. To obtain new information about the pathogenesis of acute poisoning in the rehabilitation period in 145 patients with severe acute poisoning with psychopharmacological agents (PFAp) due to the addition of pneumonia, neurotoxicants (NTp) with the development of toxic hypoxic encephalopathy and corrosive substances (CSp) with deep and widespread burns of the mucous membranes of the gastrointestinal tract, a pair correlation analysis of the block structure of the obtained correlation matrix was undertaken, establishing the relationship between the two indicators, as well as a canonical correlation analysis revealing the nature of the statistical relationship between groups of indicators, with the calculation of the canonical correlation coefficient. Results. As a result, statistically significant correlations were established between the indicators HR (viscometric, aggregation and indicators hemostasis) and ET (total and effective albumin concentration, the level of medium molecular weight peptides, the content of leukocytes, lymphocytes, neutrophils and circulating immune complexes detected in the blood, and his integral indicators) (-0.32-0.48 for PFAp, 0.29-0.35 for NTp and 0.28-(-0.51) for CSp), as well as statistically significant values canonical correlation coefficients, which indicated the development of ET due to disorders of HR. Limitations. The study was performed on laboratory data obtained during the examination of patients with acute poisoning, and therefore has no restrictions for the further use of this methodological approach in clinical trials. Conclusion. The obtained data can serve to optimize the treatment of ET in this pathology by targeted therapeutic effects on parameters of HR (on viscosity and hemostasis in PFAp and NTp, and in CSp, in addition, on aggregation).","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90269558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-28DOI: 10.47470/0869-7922-2023-31-1-18-23
T. A. Kolbasova, N. Chalisova, E. S. Egozova, Polina Nikolaevna Ivanova, K. Krasnov, Aleksandr Yakovlevich Bespalov
Introduction. Currently, the actual problem is the search for substances that can be used as drugs for the pharmacological correction of the effects of cytostatic damage by convulsive poisons. It is known that the liver is the first organ to encounter any foreign molecule carried by the portal bloodstream, and it is the most damaged. The aim of this work was to study the effect of the zinc complex of 1-butylvioluric acid on the development of an organotypic culture of rat liver tissue after poisoning with 2-(dimethylaminomethyl)phenyl ester of dimethylcarbamic acid hydrochloride. Material and methods. White 3-month-old male Wistar rats were used in the experiment. To study the effects of the test substances, liver tissue was selected and the method of organotypic cultivation was applied. Poisoning with convulsive poisons was modeled using 2-(dimethylaminomethyl)phenyl ester of dimethylcarbamic acid hydrochloride and the zinc complex of 1-butylvioluric acid was used as a drug for pharmacological correction of the effects of liver tissue damage. Results. The data obtained indicate that under the action of 2-(dimethylaminomethyl) phenyl ester of dimethylcarbamic acid hydrochloride, which simulates the effect of convulsive poisons on liver cells, their cell proliferation is inhibited. It was also found that the zinc complex of 1-butylvioluric acid eliminates the inhibitory effect of 2-(dimethylaminomethyl)phenyl ester of dimethylcarbamic acid hydrochloride on the proliferation of liver tissue culture. Research limitations. The study was performed on a culture of rat liver cells; to extrapolate data to the whole organism, it is necessary to take into account the data of toxicodynamics and toxicokinetics. Conclusion. Thus, the data obtained in the experiments prove the effectiveness of the use of the zinc complex of 1-butylvioluric acid as a drug for the pharmacological correction of the consequences of exposure to convulsive poisons, and also create a basis for its further study.
{"title":"Protective influence of the zinc complex of 1-butylvioluric acid on the development of the liver tissue culture in the presence of convulsive poisons","authors":"T. A. Kolbasova, N. Chalisova, E. S. Egozova, Polina Nikolaevna Ivanova, K. Krasnov, Aleksandr Yakovlevich Bespalov","doi":"10.47470/0869-7922-2023-31-1-18-23","DOIUrl":"https://doi.org/10.47470/0869-7922-2023-31-1-18-23","url":null,"abstract":"Introduction. Currently, the actual problem is the search for substances that can be used as drugs for the pharmacological correction of the effects of cytostatic damage by convulsive poisons. It is known that the liver is the first organ to encounter any foreign molecule carried by the portal bloodstream, and it is the most damaged. The aim of this work was to study the effect of the zinc complex of 1-butylvioluric acid on the development of an organotypic culture of rat liver tissue after poisoning with 2-(dimethylaminomethyl)phenyl ester of dimethylcarbamic acid hydrochloride. Material and methods. White 3-month-old male Wistar rats were used in the experiment. To study the effects of the test substances, liver tissue was selected and the method of organotypic cultivation was applied. Poisoning with convulsive poisons was modeled using 2-(dimethylaminomethyl)phenyl ester of dimethylcarbamic acid hydrochloride and the zinc complex of 1-butylvioluric acid was used as a drug for pharmacological correction of the effects of liver tissue damage. Results. The data obtained indicate that under the action of 2-(dimethylaminomethyl) phenyl ester of dimethylcarbamic acid hydrochloride, which simulates the effect of convulsive poisons on liver cells, their cell proliferation is inhibited. It was also found that the zinc complex of 1-butylvioluric acid eliminates the inhibitory effect of 2-(dimethylaminomethyl)phenyl ester of dimethylcarbamic acid hydrochloride on the proliferation of liver tissue culture. Research limitations. The study was performed on a culture of rat liver cells; to extrapolate data to the whole organism, it is necessary to take into account the data of toxicodynamics and toxicokinetics. Conclusion. Thus, the data obtained in the experiments prove the effectiveness of the use of the zinc complex of 1-butylvioluric acid as a drug for the pharmacological correction of the consequences of exposure to convulsive poisons, and also create a basis for its further study.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85240944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-28DOI: 10.47470/0869-7922-2023-31-1-37-46
Natal’ya Sergeevna Beloedova, T. Sinitskaya, M. A. Poroshin, Khalidya Khizbulaevna Khamidulina, Vitaly Vasilyevich Safandeev
Introduction. For the treatment of agricultural crops, an original herbicide of selective action was created - propisochlor, a derivative of chloroacetanilide. Its characteristics in an acute toxicological experiment didn’t reveal the features of the pathogenesis of intoxication. The identification of regularities in the manifestation of the toxic properties of propisochlor in various regimens with the oral route of exposure is necessary at the stage of production design. Moreover, it is necessary to substantiate a number of hygienic regulations for safe production and its further application in agriculture, which lies in the plane of solving the leading state tasks aimed at protecting human health and its environment, and meets the requirements of international legislation. A special role in the development of such methods and methods belongs to the sanitary-toxicological study of new xenobiotics and generic molecules, as a result of which threshold and subthreshold doses of pesticide preparations and their active substances are determined. The aim of this study was to characterize propisochlor in a chronic oral toxicology study in rats. To achieve the goal, it was necessary to solve the following tasks: to study the chronic oral effect of the chloroacetanilide derivative on the rat organism; establish a dose that does not have a visible undesirable effect (NOELch); set the lowest dose at which no adverse effects are observed (LOAELch); calculate the allowable daily intake, or allowable daily exposure (ADD, or ADI, or PDE) for a person. Material and methods. The object of testing in this work was a herbicide from the class of chloroacetanilide, propisochlor. The test system in the chronic experiment was white male rats, on which the influence of the test compound was evaluated in dynamics after 1, 3, 6 and 12 months according to the state of integral indicators. Results. The parameters of the oral toxicity of the test compound were determined and the changes in the studied integral indicators were evaluated at various stages of the experiment in a chronic experiment. Conclusion. Based on the comparative characterization of a new herbicide propisochlor in a chronic oral toxicology study in rats, a non-acting dose (NOEL), the lowest effective dose (LOAEL), and an acceptable daily dose for humans (ADI, or PDE) are justified.
{"title":"Characterization of a chloroacetanilide derivative in a chronic oral toxicology study in rats","authors":"Natal’ya Sergeevna Beloedova, T. Sinitskaya, M. A. Poroshin, Khalidya Khizbulaevna Khamidulina, Vitaly Vasilyevich Safandeev","doi":"10.47470/0869-7922-2023-31-1-37-46","DOIUrl":"https://doi.org/10.47470/0869-7922-2023-31-1-37-46","url":null,"abstract":"Introduction. For the treatment of agricultural crops, an original herbicide of selective action was created - propisochlor, a derivative of chloroacetanilide. Its characteristics in an acute toxicological experiment didn’t reveal the features of the pathogenesis of intoxication. The identification of regularities in the manifestation of the toxic properties of propisochlor in various regimens with the oral route of exposure is necessary at the stage of production design. Moreover, it is necessary to substantiate a number of hygienic regulations for safe production and its further application in agriculture, which lies in the plane of solving the leading state tasks aimed at protecting human health and its environment, and meets the requirements of international legislation. A special role in the development of such methods and methods belongs to the sanitary-toxicological study of new xenobiotics and generic molecules, as a result of which threshold and subthreshold doses of pesticide preparations and their active substances are determined. The aim of this study was to characterize propisochlor in a chronic oral toxicology study in rats. To achieve the goal, it was necessary to solve the following tasks: to study the chronic oral effect of the chloroacetanilide derivative on the rat organism; establish a dose that does not have a visible undesirable effect (NOELch); set the lowest dose at which no adverse effects are observed (LOAELch); calculate the allowable daily intake, or allowable daily exposure (ADD, or ADI, or PDE) for a person. Material and methods. The object of testing in this work was a herbicide from the class of chloroacetanilide, propisochlor. The test system in the chronic experiment was white male rats, on which the influence of the test compound was evaluated in dynamics after 1, 3, 6 and 12 months according to the state of integral indicators. Results. The parameters of the oral toxicity of the test compound were determined and the changes in the studied integral indicators were evaluated at various stages of the experiment in a chronic experiment. Conclusion. Based on the comparative characterization of a new herbicide propisochlor in a chronic oral toxicology study in rats, a non-acting dose (NOEL), the lowest effective dose (LOAEL), and an acceptable daily dose for humans (ADI, or PDE) are justified.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88310626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-28DOI: 10.47470/0869-7922-2023-31-1-47-53
L. Valiullin, Leysan Maratovna Timerbulatova, Vladislav Ivanovich Egorov, F. R. Zaripov, I. Raginov, Aleksey Anatolevich Nabatov
Introduction. The testing for mitochondrial dysfunction has become routine assay for drug and cosmetics safety evaluation. Mitochondria are targets of many pharmaceutical and therapeutic agents that can damage them and lead to changes in morphology and function. Spermatozoa have one of the highest ratios of mitochondria to body size, they lack the cytoplasm between the mitochondria and the plasma membrane, which makes them a good potential model for a rapid test on mitochondrial toxicity. The aim of our work - assessment of motility and mitochondrial membrane potential of bovine spermatozoa Bos taurus taurus in the presence of T-2-toxin and deltamethrin. Material and methods. T-2-toxin and deltamethrin were used as toxins. The main parameters studied were the level of mitochondrial potential (using the MitoTracker™ Green FM dye), sperm motility and their relationship. Results. We found a strong correlation between the motility of bovine spermatozoa and the mitochondrial potential of their mitochondria (R>0.87; p<0.05). The mitochondrial toxicity of deltamethrin has been confirmed, although to a much lesser extent than that of the T-2-toxin. In addition, certain patterns were found in the distribution of active zones of the mitochondrial potential in bull spermatozoa. Conclusion. Using deltamethrin and T-2-toxin in this study, it was shown that the sperm cells of bulls and their mitochondrial potential can be used as an express test for mitochondrial toxicity. Limitations. Determination of the mitochondrial potential of the studied spretamotozoa using the MitoTracker™ dye was rather of a qualitative nature, reflecting not so much the level of the mitochondrial potential but the number of spermatozoa that have the potential sufficient to initiate the luminescence of the dye.
{"title":"Use of bovine spermatozoa as a rapid test for mitochondrial toxicity of T-2-toxin and deltamethrin","authors":"L. Valiullin, Leysan Maratovna Timerbulatova, Vladislav Ivanovich Egorov, F. R. Zaripov, I. Raginov, Aleksey Anatolevich Nabatov","doi":"10.47470/0869-7922-2023-31-1-47-53","DOIUrl":"https://doi.org/10.47470/0869-7922-2023-31-1-47-53","url":null,"abstract":"Introduction. The testing for mitochondrial dysfunction has become routine assay for drug and cosmetics safety evaluation. Mitochondria are targets of many pharmaceutical and therapeutic agents that can damage them and lead to changes in morphology and function. Spermatozoa have one of the highest ratios of mitochondria to body size, they lack the cytoplasm between the mitochondria and the plasma membrane, which makes them a good potential model for a rapid test on mitochondrial toxicity. The aim of our work - assessment of motility and mitochondrial membrane potential of bovine spermatozoa Bos taurus taurus in the presence of T-2-toxin and deltamethrin. Material and methods. T-2-toxin and deltamethrin were used as toxins. The main parameters studied were the level of mitochondrial potential (using the MitoTracker™ Green FM dye), sperm motility and their relationship. Results. We found a strong correlation between the motility of bovine spermatozoa and the mitochondrial potential of their mitochondria (R>0.87; p<0.05). The mitochondrial toxicity of deltamethrin has been confirmed, although to a much lesser extent than that of the T-2-toxin. In addition, certain patterns were found in the distribution of active zones of the mitochondrial potential in bull spermatozoa. Conclusion. Using deltamethrin and T-2-toxin in this study, it was shown that the sperm cells of bulls and their mitochondrial potential can be used as an express test for mitochondrial toxicity. Limitations. Determination of the mitochondrial potential of the studied spretamotozoa using the MitoTracker™ dye was rather of a qualitative nature, reflecting not so much the level of the mitochondrial potential but the number of spermatozoa that have the potential sufficient to initiate the luminescence of the dye.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"67 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83297845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-28DOI: 10.47470/0869-7922-2023-31-1-30-36
L. V. Shabasheva, G. Protasova, V. B. Popov
Introduction. The effect of carbon tetrachloride (freon-10, asordin, hladon-10) is an organochlorine compound with the chemical formula CCl4 and the subsequent transplantation of fetal liver cells (FLC) on DNA degradation and repair in rat hepatocytes by means of alkaline single-cell gel electrophoresis (DNA comet assay) was assessed. Material and methods. Acute toxic damage to the rat liver was simulated by a single oral administration to female Wistar rats of CCl4 in an oil solution at a dose of 3000 mg/kg. As a protective agent, a suspension of FLC of E19 rat fetuses was used. Quantitative assessment of the degree of damage to the nuclear DNA of liver cells was performed by DNA comet assay on days 1, 3, 5, 7 and 16 of the experiment. Results. Intravenous injections of fetal liver cells 6 h after exposure to CCl4 induces DNA repair processes in rat hepatocytes in 5-7 days and led to a decrease in the intensity of nuclear DNA damage. The trend toward a decrease in the number of undamaged hepatocytes continued on the 16th day of the experiment, and, therewith, the enhancement of reparative processes after FLC injection revealed itself in in a significant decrease in the number of hepatocytes with a high intensity of nuclear DNA damage. Limitations. To prevent unwanted death of animals in the group, studies were limited to a dose of 3000 mg/kg of CCl4 in oil solution. Conclusion. The method of alkaline single-cell gel electrophoresis (DNA comet assay) allowed quantitative assessment of the degrees of genome damage and repair. The obtained positive results suggest that FLC exert a protective effect of the structure of the DNA of rat liver role after acute exposure to CCl4.
{"title":"Assessment of the effect of cell transplantation on DNA repair in rat hepatocytes exposed to carbon tetrachloride (CCl4) by DNA comet assay","authors":"L. V. Shabasheva, G. Protasova, V. B. Popov","doi":"10.47470/0869-7922-2023-31-1-30-36","DOIUrl":"https://doi.org/10.47470/0869-7922-2023-31-1-30-36","url":null,"abstract":"Introduction. The effect of carbon tetrachloride (freon-10, asordin, hladon-10) is an organochlorine compound with the chemical formula CCl4 and the subsequent transplantation of fetal liver cells (FLC) on DNA degradation and repair in rat hepatocytes by means of alkaline single-cell gel electrophoresis (DNA comet assay) was assessed. Material and methods. Acute toxic damage to the rat liver was simulated by a single oral administration to female Wistar rats of CCl4 in an oil solution at a dose of 3000 mg/kg. As a protective agent, a suspension of FLC of E19 rat fetuses was used. Quantitative assessment of the degree of damage to the nuclear DNA of liver cells was performed by DNA comet assay on days 1, 3, 5, 7 and 16 of the experiment. Results. Intravenous injections of fetal liver cells 6 h after exposure to CCl4 induces DNA repair processes in rat hepatocytes in 5-7 days and led to a decrease in the intensity of nuclear DNA damage. The trend toward a decrease in the number of undamaged hepatocytes continued on the 16th day of the experiment, and, therewith, the enhancement of reparative processes after FLC injection revealed itself in in a significant decrease in the number of hepatocytes with a high intensity of nuclear DNA damage. Limitations. To prevent unwanted death of animals in the group, studies were limited to a dose of 3000 mg/kg of CCl4 in oil solution. Conclusion. The method of alkaline single-cell gel electrophoresis (DNA comet assay) allowed quantitative assessment of the degrees of genome damage and repair. The obtained positive results suggest that FLC exert a protective effect of the structure of the DNA of rat liver role after acute exposure to CCl4.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87056844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-28DOI: 10.47470/0869-7922-2023-31-1-24-29
M. E. Shemaev, Alexandr Mikhajlovich Malov, R. K. Glushkov, K. Krasnov, Dmitrij Konstantinovich Shchegolihin, N. Lapina
Introduction. Heavy metals have a serious toxic effect on the human body. The availability of adequate models for the elimination of toxicants and the testing of enterosorbents based on them will improve the quality of poisoning therapy. Material and methods. To assess the effectiveness of the sorbent, a formalized model based on data on the cumulative excretion of cadmium in urine and feces for 20 days was used. Intramuscular priming with cadmium acetate was carried out during the first three days of the experiment at a daily dose of 3 mg/ kg, the enterosorbent was administered orally at a dose of 100 mg/kg during the study. The cadmium content in the biological media was determined by methods of inversion voltammetry. Results. During the experiment, no more than 3% of the injected toxicant was removed from the animals of both groups. The enterosorbent in the conditions of the experiment did not change the amount of cadmium excreted, but affected the redistribution between the renal and intestinal elimination streams. A significant effect of the enterosorbent on the cadmium content in the liver was noted. Limitations. Evaluation of the effect of the drug on the elimination of the toxicant was carried out for a limited period of time. Additional experiments with longer observation periods and other metals and their dosages would allow to reveal in more detail the beneficial properties of the studied drug. Conclusion. A significant effect of the enterosorbent on the cadmium content in the liver was noted. There may be a secondary intake of cadmium into the blood from the intestine and a negative effect of this process on kidneys.
{"title":"Research of the alginate-pectin sorbent influence on the elimination of cadmium from the body of rats","authors":"M. E. Shemaev, Alexandr Mikhajlovich Malov, R. K. Glushkov, K. Krasnov, Dmitrij Konstantinovich Shchegolihin, N. Lapina","doi":"10.47470/0869-7922-2023-31-1-24-29","DOIUrl":"https://doi.org/10.47470/0869-7922-2023-31-1-24-29","url":null,"abstract":"Introduction. Heavy metals have a serious toxic effect on the human body. The availability of adequate models for the elimination of toxicants and the testing of enterosorbents based on them will improve the quality of poisoning therapy. Material and methods. To assess the effectiveness of the sorbent, a formalized model based on data on the cumulative excretion of cadmium in urine and feces for 20 days was used. Intramuscular priming with cadmium acetate was carried out during the first three days of the experiment at a daily dose of 3 mg/ kg, the enterosorbent was administered orally at a dose of 100 mg/kg during the study. The cadmium content in the biological media was determined by methods of inversion voltammetry. Results. During the experiment, no more than 3% of the injected toxicant was removed from the animals of both groups. The enterosorbent in the conditions of the experiment did not change the amount of cadmium excreted, but affected the redistribution between the renal and intestinal elimination streams. A significant effect of the enterosorbent on the cadmium content in the liver was noted. Limitations. Evaluation of the effect of the drug on the elimination of the toxicant was carried out for a limited period of time. Additional experiments with longer observation periods and other metals and their dosages would allow to reveal in more detail the beneficial properties of the studied drug. Conclusion. A significant effect of the enterosorbent on the cadmium content in the liver was noted. There may be a secondary intake of cadmium into the blood from the intestine and a negative effect of this process on kidneys.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82673723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-30DOI: 10.47470/0869-7922-2022-30-6-351-358
A. Kamalova, Galina Alekseevna Garina, Yu.A. Kadyrova, R. A. Nizamova, Madina Shigapovna Zainetdinova, E. M. Kvitko
Introduction. Acute exposure to chemicals is the most common cause of poisoning in pediatric practice and one of the leading causes of morbidity and mortality worldwide [1]. In the available domestic literature, we have not found publications concerning up-to-date data on the etiological structure, clinical characteristics of patients and outcomes of acute poisoning in children. Knowledge of clinical manifestations and prognosis for various poisoning in children will help doctors of the outpatient level and the reception department of hospitals to quickly determine the tactics of patient management and prevent serious consequences. Material and methods. In this retrospective study, the case histories of 300 children aged 0 to 18 years who were admitted to the emergency department of the third - level hospital - the Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan with acute poisoning for the period from 2018 to 2020 were studied. Results. The study included 176 boys (58.6%) and 124 girls (41.4%). Poisoning was most common in the age periods from 1 to 3 years - 127 (42.3%) and from 12 to 18 years - 76 (25.3%). 67% of poisoning were unintentional, and in 33% of cases - intentional. The largest number of poisonings - 248 (82.7%) occurred at home, and 52 (17.3%) were poisoned outside the home. Of the 300 cases of poisoning, 70 (23.3%) were of mild severity, 151 (50.3%) of moderate severity, 79 (26.3%) of severe severity. The most common toxic substances were: chemical detergents, carbon monoxide, vasoconstrictor drugs, nonsteroidal anti-inflammatory drugs. All 300 patients survived. Limitations of the study. The data of patients living in the Republic of Tatarstan who were admitted to the emergency department of the DRKB for the time period from 2018 to 2020 were studied. Conclusion. Over the past 2 years, there has been an increase in the frequency of poisoning in the city of Kazan. Most patients had mild to moderate poisoning, more often unintentional. A serious condition was observed in adolescents when the cause of poisoning was a suicide attempt. The increase in the number of poisonings can be associated with the over-the-counter sale of a large number of drugs, their aggressive advertising, as well as improper storage at home.
{"title":"Acute poisoning in children: a retrospective case study","authors":"A. Kamalova, Galina Alekseevna Garina, Yu.A. Kadyrova, R. A. Nizamova, Madina Shigapovna Zainetdinova, E. M. Kvitko","doi":"10.47470/0869-7922-2022-30-6-351-358","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-6-351-358","url":null,"abstract":"Introduction. Acute exposure to chemicals is the most common cause of poisoning in pediatric practice and one of the leading causes of morbidity and mortality worldwide [1]. In the available domestic literature, we have not found publications concerning up-to-date data on the etiological structure, clinical characteristics of patients and outcomes of acute poisoning in children. Knowledge of clinical manifestations and prognosis for various poisoning in children will help doctors of the outpatient level and the reception department of hospitals to quickly determine the tactics of patient management and prevent serious consequences. Material and methods. In this retrospective study, the case histories of 300 children aged 0 to 18 years who were admitted to the emergency department of the third - level hospital - the Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan with acute poisoning for the period from 2018 to 2020 were studied. Results. The study included 176 boys (58.6%) and 124 girls (41.4%). Poisoning was most common in the age periods from 1 to 3 years - 127 (42.3%) and from 12 to 18 years - 76 (25.3%). 67% of poisoning were unintentional, and in 33% of cases - intentional. The largest number of poisonings - 248 (82.7%) occurred at home, and 52 (17.3%) were poisoned outside the home. Of the 300 cases of poisoning, 70 (23.3%) were of mild severity, 151 (50.3%) of moderate severity, 79 (26.3%) of severe severity. The most common toxic substances were: chemical detergents, carbon monoxide, vasoconstrictor drugs, nonsteroidal anti-inflammatory drugs. All 300 patients survived. Limitations of the study. The data of patients living in the Republic of Tatarstan who were admitted to the emergency department of the DRKB for the time period from 2018 to 2020 were studied. Conclusion. Over the past 2 years, there has been an increase in the frequency of poisoning in the city of Kazan. Most patients had mild to moderate poisoning, more often unintentional. A serious condition was observed in adolescents when the cause of poisoning was a suicide attempt. The increase in the number of poisonings can be associated with the over-the-counter sale of a large number of drugs, their aggressive advertising, as well as improper storage at home.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88972353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-30DOI: 10.47470/0869-7922-2022-30-6-370-376
S. V. Masolitin, D. Protsenko, I. N. Tyurin, O. Mamontova, M. Magomedov, T. Kim, A. V. Marukhov, N. V. Chubchenko
Introduction. The prevalence of rhabdomyolysis among people admitted to the hospital due to acute poisoning reaches, according to various foreign sources, from 30 to 40%. In 60% of cases, the development of rhabdomyolysis in adult patients is associated with acute exogenous intoxication. Currently, data on the prevalence, structure and outcomes of treatment of rhabdomyolysis in toxicological patients are mainly presented by the results of foreign clinical and epidemiological studies. The aim is to study the prevalence, structure, frequency of complications and outcomes of treatment of rhabdomyolysis in acute exogenous intoxication in a multidisciplinary hospital. Material and methods. The study included 1,363 patients who were treated from 2017 to 2020 with acute exogenous intoxication. During the study, 98 patients with rhabdomyolysis were selected from the general group. The frequency of poisoning with various toxicants was analyzed, the effects of which led to the development of rhabdomyolysis in acute exogenous intoxication. The incidence of acute kidney injury (AKI) was detected, the outcomes of acute poisoning treatment, the duration of inpatient treatment were determined, and a comparative analysis was carried out between groups of patients with rhabdomyolysis in acute exogenous intoxication (n=98) and without it (n=1265). Results. The prevalence of rhabdomyolysis among patients hospitalized for acute poisoning was 7%. The main reason for the development of rhabdomyolysis was the use of narcotic drugs - 87% of cases. The development of rhabdomyolysis in acute exogenous intoxication in 59.2% of cases is accompanied by the occurrence of AKI, which is significantly higher than among patients without rhabdomyolysis (11.6%). The occurrence of rhabdomyolysis in toxicological patients increases hospital mortality from 6.1 to 10.2%, as well as the duration of inpatient treatment and intensive care by 5.2 and 3.3 days, respectively. Limitations. The study was conducted based on only one multidisciplinary hospital in Moscow in the period from 2017 to 2020. Conclusion. Rhabdomyolysis is a serious complication of acute poisoning, the development of which significantly worsens the outcomes of treatment of patients with a toxicological profile, which requires the development of effective methods for the prevention, diagnosis and treatment of rhabdomyolysis in acute exogenous intoxication.
{"title":"Prevalence, structure, frequency of complications and outcomes of treatment of rhabdomyolysis in acute exogenous intoxication in a multidisciplinary hospital","authors":"S. V. Masolitin, D. Protsenko, I. N. Tyurin, O. Mamontova, M. Magomedov, T. Kim, A. V. Marukhov, N. V. Chubchenko","doi":"10.47470/0869-7922-2022-30-6-370-376","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-6-370-376","url":null,"abstract":"Introduction. The prevalence of rhabdomyolysis among people admitted to the hospital due to acute poisoning reaches, according to various foreign sources, from 30 to 40%. In 60% of cases, the development of rhabdomyolysis in adult patients is associated with acute exogenous intoxication. Currently, data on the prevalence, structure and outcomes of treatment of rhabdomyolysis in toxicological patients are mainly presented by the results of foreign clinical and epidemiological studies. The aim is to study the prevalence, structure, frequency of complications and outcomes of treatment of rhabdomyolysis in acute exogenous intoxication in a multidisciplinary hospital. Material and methods. The study included 1,363 patients who were treated from 2017 to 2020 with acute exogenous intoxication. During the study, 98 patients with rhabdomyolysis were selected from the general group. The frequency of poisoning with various toxicants was analyzed, the effects of which led to the development of rhabdomyolysis in acute exogenous intoxication. The incidence of acute kidney injury (AKI) was detected, the outcomes of acute poisoning treatment, the duration of inpatient treatment were determined, and a comparative analysis was carried out between groups of patients with rhabdomyolysis in acute exogenous intoxication (n=98) and without it (n=1265). Results. The prevalence of rhabdomyolysis among patients hospitalized for acute poisoning was 7%. The main reason for the development of rhabdomyolysis was the use of narcotic drugs - 87% of cases. The development of rhabdomyolysis in acute exogenous intoxication in 59.2% of cases is accompanied by the occurrence of AKI, which is significantly higher than among patients without rhabdomyolysis (11.6%). The occurrence of rhabdomyolysis in toxicological patients increases hospital mortality from 6.1 to 10.2%, as well as the duration of inpatient treatment and intensive care by 5.2 and 3.3 days, respectively. Limitations. The study was conducted based on only one multidisciplinary hospital in Moscow in the period from 2017 to 2020. Conclusion. Rhabdomyolysis is a serious complication of acute poisoning, the development of which significantly worsens the outcomes of treatment of patients with a toxicological profile, which requires the development of effective methods for the prevention, diagnosis and treatment of rhabdomyolysis in acute exogenous intoxication.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83173712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-30DOI: 10.47470/0869-7922-2022-30-6-377-385
N. A. Goryacheva, Dmitrij Ivanovic Rzhevskiy, Gulsara Amsngalievna Slashheva, N. I. Novikova, Mikhail Valentinivich Kisilevskiy, I. Chikileva, Rajmonda Yanovna Vlasenko, I. A. Dyachenko, A. N. Murashev, Dmitrij Aleksandrovich Bondarenko
Introduction. The Car-T-cell therapy is current and modern promising method for the oncology treatment. USA Food and Drug Sanitary Control Department confirms six drugs for cellular immunotherapy the blood oncology today. But the information about biomedical product preclinical test is absent, because used T-cells (cell with chimeric antigen receptor) are autologous for humans, which is the problem for use classic toxicity tests. Besides the biomedical product safety becomes questionable, therefore the different preclinical research strategy is developed to solve those problems and produce normal test-systems with therapeutic target. The aim of the study was to evaluate the acute toxicity in immunodeficient BALB/c Nude mice of an antineoplastic drug based on genetically modified T/NK cells that express a chimeric T-cell anti-HER2 receptor. Material and methods. Test and control groups consisted of five males and five females. Animals were injected a single intravenous or intraperitoneal injection of the testing product and the solvent-cryopreserving carrier at the dose 0,2 ml/animal. There were two doses: equal to the human therapeutic 0,5•106 cell/animal dose and ten times over then the therapeutic dose 5•106 cell/animal. During the test the animal’s weight, the food intake and clinically symptoms of the testing product toxicity were registered. On the fifteenth of the study day animals were euthanatized and exposed to a necropsy with the organs’ macroscopic inspection, the weighting and fixating. The detection of the testing biomedical product toxicity was the aim of the histology analysis. Results. A single intravenous or intraperitoneal injection of the biomedical product «anti-HER2-CAR-T/ CAR-NK» at the human therapeutic dose, as well as in 10 times more than the same, is safe for BALB/c Nude mice. The preclinical study has shown the absence of significant toxic effects. Limitations. The research was performed on Balb/c nude line immunodeficient mice, because the tested product contained living foreign cells. Conclusion. This work can be the main basis for the creation of biomedical product preclinical research protocol of biomedical cell products produced from CAR-technology.
介绍。car - t细胞疗法是目前最具发展前景的肿瘤治疗方法。美国食品和药物卫生控制部门今天确认了六种用于细胞免疫治疗血液肿瘤的药物。但由于使用的t细胞(嵌合抗原受体细胞)对人体来说是自体的，这是传统的毒性试验存在的问题，因此缺乏生物医学产品临床前试验的相关信息。此外，生物医药产品的安全性也受到质疑，因此，人们制定了不同的临床前研究策略来解决这些问题，并生产出具有治疗目标的正常试验系统。该研究的目的是评估一种基于表达嵌合T细胞抗her2受体的转基因T/NK细胞的抗肿瘤药物对免疫缺陷BALB/c裸鼠的急性毒性。材料和方法。实验组和对照组分别为5名男性和5名女性。动物单次静脉或腹腔注射试验品和溶剂-低温保存载体，剂量为0.2 ml/只。有两种剂量:等于人类治疗剂量0,5•106细胞/动物和10倍以上的治疗剂量5•106细胞/动物。试验期间记录动物体重、摄食量和试验产品毒性的临床症状。在研究当天的第15天，对动物实施安乐死，并进行尸检，对器官进行肉眼检查，称重和固定。组织学分析的目的是检测被试生物制品的毒性。结果。单次静脉或腹腔注射人体治疗剂量的生物医学产品“抗her2 - car - t / CAR-NK”，以及10倍以上的剂量，对BALB/c裸鼠是安全的。临床前研究显示没有明显的毒性作用。的局限性。本研究是在Balb/c裸系免疫缺陷小鼠身上进行的，因为被测产品含有活的外源细胞。结论。本工作可为car技术生产的生物医学细胞产品临床前研究方案的制定提供主要依据。
{"title":"Preclinical acute toxicity studies of the CAR technology products for malignant neoplasms therapy on the example of the «anti-HER2-CAR-T/CAR-NK»","authors":"N. A. Goryacheva, Dmitrij Ivanovic Rzhevskiy, Gulsara Amsngalievna Slashheva, N. I. Novikova, Mikhail Valentinivich Kisilevskiy, I. Chikileva, Rajmonda Yanovna Vlasenko, I. A. Dyachenko, A. N. Murashev, Dmitrij Aleksandrovich Bondarenko","doi":"10.47470/0869-7922-2022-30-6-377-385","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-6-377-385","url":null,"abstract":"Introduction. The Car-T-cell therapy is current and modern promising method for the oncology treatment. USA Food and Drug Sanitary Control Department confirms six drugs for cellular immunotherapy the blood oncology today. But the information about biomedical product preclinical test is absent, because used T-cells (cell with chimeric antigen receptor) are autologous for humans, which is the problem for use classic toxicity tests. Besides the biomedical product safety becomes questionable, therefore the different preclinical research strategy is developed to solve those problems and produce normal test-systems with therapeutic target. The aim of the study was to evaluate the acute toxicity in immunodeficient BALB/c Nude mice of an antineoplastic drug based on genetically modified T/NK cells that express a chimeric T-cell anti-HER2 receptor. Material and methods. Test and control groups consisted of five males and five females. Animals were injected a single intravenous or intraperitoneal injection of the testing product and the solvent-cryopreserving carrier at the dose 0,2 ml/animal. There were two doses: equal to the human therapeutic 0,5•106 cell/animal dose and ten times over then the therapeutic dose 5•106 cell/animal. During the test the animal’s weight, the food intake and clinically symptoms of the testing product toxicity were registered. On the fifteenth of the study day animals were euthanatized and exposed to a necropsy with the organs’ macroscopic inspection, the weighting and fixating. The detection of the testing biomedical product toxicity was the aim of the histology analysis. Results. A single intravenous or intraperitoneal injection of the biomedical product «anti-HER2-CAR-T/ CAR-NK» at the human therapeutic dose, as well as in 10 times more than the same, is safe for BALB/c Nude mice. The preclinical study has shown the absence of significant toxic effects. Limitations. The research was performed on Balb/c nude line immunodeficient mice, because the tested product contained living foreign cells. Conclusion. This work can be the main basis for the creation of biomedical product preclinical research protocol of biomedical cell products produced from CAR-technology.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88743670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-30DOI: 10.47470/0869-7922-2022-30-6-403-413
Khalidya Khizbulaevna Khamidulina, E. Tarasova, Mikhail Leonidovich Lastovetskiy
Introduction. The introduction of new chemical products to the market requires a preliminary assessment of their danger to human health and the environment, including specific and long-term effects. Taking into account the medical and social significance of the consequences of exposure to chemicals with a mutagenic effect on the body, the study of genotoxicity / mutagenicity seems to be extremely relevant. In order to reduce the number of experiments performed on animals, calculation methods are being actively introduced into toxicological practice, in particular OECD QSAR Toolbox software. Therefore, the aim of our research was to study the possibility of using the OECD QSAR Toolbox software to predict the mutagenic effects of chemicals. Material and methods. OECD QSAR Toolbox software version 4.4.1., OECD guidelines on the assessment of the mutagenic effect. Results and discussion. We have developed the “Guidelines for predicting the mutagenic effects of chemicals”, which includes a detailed description and work with the program when predicting the mutagenic effects of chemicals. Based on the analysis of OECD documents on the assessment of the mutagenic potential of chemicals, seven most widely used tests were selected, which allow evaluating the effect on various test objects in the presence / absence of metabolic activation systems. For methods, indicators were selected that must be set to start the calculation in the QSAR Toolbox software. The most suitable databases and profilers were also indentified. Conclusion. Forecasting using the OECD QSAR Toolbox software is a screening method that involves performing several calculations using the results of various experimental studies for analogs, and subsequent expert interpretation of the data obtained.
{"title":"Application of OECD QSAR Toolbox software for predicting the mutagenic effects of chemicals","authors":"Khalidya Khizbulaevna Khamidulina, E. Tarasova, Mikhail Leonidovich Lastovetskiy","doi":"10.47470/0869-7922-2022-30-6-403-413","DOIUrl":"https://doi.org/10.47470/0869-7922-2022-30-6-403-413","url":null,"abstract":"Introduction. The introduction of new chemical products to the market requires a preliminary assessment of their danger to human health and the environment, including specific and long-term effects. Taking into account the medical and social significance of the consequences of exposure to chemicals with a mutagenic effect on the body, the study of genotoxicity / mutagenicity seems to be extremely relevant. In order to reduce the number of experiments performed on animals, calculation methods are being actively introduced into toxicological practice, in particular OECD QSAR Toolbox software. Therefore, the aim of our research was to study the possibility of using the OECD QSAR Toolbox software to predict the mutagenic effects of chemicals. Material and methods. OECD QSAR Toolbox software version 4.4.1., OECD guidelines on the assessment of the mutagenic effect. Results and discussion. We have developed the “Guidelines for predicting the mutagenic effects of chemicals”, which includes a detailed description and work with the program when predicting the mutagenic effects of chemicals. Based on the analysis of OECD documents on the assessment of the mutagenic potential of chemicals, seven most widely used tests were selected, which allow evaluating the effect on various test objects in the presence / absence of metabolic activation systems. For methods, indicators were selected that must be set to start the calculation in the QSAR Toolbox software. The most suitable databases and profilers were also indentified. Conclusion. Forecasting using the OECD QSAR Toolbox software is a screening method that involves performing several calculations using the results of various experimental studies for analogs, and subsequent expert interpretation of the data obtained.","PeriodicalId":23128,"journal":{"name":"Toxicological Review","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91428642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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