Participation of Free-Radical Processes in Structural and Metabolic Disturbances in the Lung Tissues Caused by Exposure to Coal-Rock Dust and their Adaptogenic Correction.

Adaptive correction of structural and metabolic disturbances in the lungs caused by longterm exposure to coal-rock dust were studied in experiments on rats. It was shown that the complex antioxidant preparation containing dihydroquercetin compensated disturbances in the redox balance in the lung tissue, prevented the formation of dust granulomas, and reduced the severity of degenerative changes in the bronchopulmonary system.

[Hygienic standardization of 2-formylphenoxyethane acid in the air of the working zone].

The toxic properties of 2-formylphenoxyethane acid for hygienic standardization in the air of working zone were studied. The substance in the dose equal of DL introduced into the stomach for male rats, male and female mice accounted for 5354, 3698 and 4322 mg/kg. It refers to moderately hazardous substances. No significant differences in species and gender sensitivity of animals to the substance were noted. It possesses a strong ability to cumulation: C is 2.9. It has a marked irritating effect to the mucous membranes of eyes and the moderate one - to the skin. Ithas a toxic effect on the liver, kidneys, central nervous system. The threshold of acute inhalation effect (Lim) is 120.3 mg/m. At Lim level it has no irritating effect on the respiratory tract. The tentative safe exposure level of 2-formylphenoxyethane acid in the air of working zone is 1 mg/m.

Experimental studies of intracellular liver protective mechanisms in development of chronic fluorine intoxication.

The authors studied intracellular liver protective mechanisms in development of chronic fluorine intoxication. Findings are that synthesis of protective proteins HIF-1α, HOx-1, HOx-2 and HSP72, restricting free radical oxidation in hepatocytes increased in liver at early stages (1-3 weeks) of exposure to fluorine. At late terms of chronic fluorine intoxication (6-12 weeks), damaging effects of fluorine result from its genotixicity - ability to suppress synthesis of intracellular protective proteins and enzymes of main metabolic cycles in liver.

On hygienic regulation of benzodiazepines.

Experimental studies covered risk of possible toxic influence by medications - derivatives of 1.4-benzodiazepine - in single and multiple intake by intragastric way, inhalation and skin application. The authors give recommendations on hygienic regulation of 1.4-benzodiazepine derivatives - alprazolam, diazepam, mezapam and nozepam. The study results served as a base for specifying approximate safe level of exposure to alprazolam at level of 0.1 mg/m³, diazepam - 0.2 mg/m³, mezapam - 0.3 mg/m³ and nozepam at level of 1.0 mg/m³ in the air of workplace.

[Hygienic standardization of 2-formylphenoxyethane acid in the air of the working zone Hygiene of Children and Adolescents].

The toxic properties of 2-formylphenoxyethane acid for hygienic standardization in the air of the working zone were studied. DL of the substance under the introduction into the stomach for male rats, male and female mice was 5354, 3698 and 4322 mg/kg. This compound refers to moderately hazardous substances. No significant differences in species and gender sensitivity of animals to the substance were found. This compound possesses a strong ability to the accumulation: C accounts of 2.9. It has a marked irritating effect to the mucous membranes of eyes and the moderate impact to the skin. It has a toxic effect on the liver, kidneys, central nervous system. The threshold of acute inhalation effect (Lim) equals to 120.3 mg/m. It has no irritating effect to the respiratory tract at Lim level. The tentative safe exposure level of 2-formylphenoxyethane acid in the air of working zone equals to 1 mg/m.

[Toxicological characteristics of the cinnamic].

The toxic properties of the cinnamic alcohol with an aim of its hygienic rating are studied. DL for male rats, male and female mice are respectively 3300, 3000 and 2700 mg/kg. It refers to the substances of hazard class 3. The clinical picture of acute poisoning was characterized by the general depression, muscle relaxation, disorder of the movement coordination, decrease in body temperature and death in the first and the second days after the poisoning. The differences in sex and species sensitivity of the animals to the substance are not observed: the rates of species differences and sex sensitivity are ~1. Single and repeated (10 days) inhalation of the vapors of the cinnamic alcohol at the greatest possible saturation neither cause the death of mice no signs of toxicity. It has a weak ability to cumulation: the cumulation coefficient is 5.4. It has no local irritating action to the skin. Skin-resorptive and sensitizing effects are not revealed. It has a weak irritating effect on the mucous membranes of the eyes. In the subacute experiment after the introduction of the substance into the stomach in a total dose equal to 5.2 DL we noted the lag of the experimental animals in body weight gain from the control ones, the increase in the activity of y-glutamyl transpeptidase and transaminases in serum. In the peripheral blood the decrease in hemoglobin, erythrocytes and eosinophils count is revealed. The threshold of the acute inhalation effect is 140 mg/m (by the reduction in the number of erythrocytes and hemoglobin in peripheral blood). Tentative safe level of the exposure to the cinnamic alcohol in the air of the working zone is 5 mg/m (vapors).

Experimental Study of the Mechanisms of Intracellular Defense in Cardiomyocytes Associated with Stages of Anthracosilicosis Development.

Mechanisms of intracellular defense of rat cardiomyocytes were studied in dynamics of anthracosilicosis development induced by long-term inhalation of coal and rock dust. It was shown that synthesis of transcription factor HIF-1α and protective proteins increased in the heart at the early stages of coal and rock dust inhalation (1-3 weeks), and these changes limited the development of free radical oxidation and activated metabolism of glucose and fatty acids. Exposure to coal and rock dust for 6-12 weeks activated free radical oxidation and decreased basal metabolism in cardiomyocytes.

[Toxicity assessment of sulpiride as the basis of its hygienic standardization].

Toxic properties of sulpiride were studied with an aim of its hygienic standardization. LD50 of sulpiride in administration into the stomach of male rats and mice is 7200 and 3400 mg/kg, for female rats and mice - 6000 and 2300 mg/kg. It refers to substances of hazard Classes 3, 4. No significant differences were noted in the species and sex sensitivity of animals to a substance. In intraperitoneal administration LD50 for male rats is 220 mg/kg, for female rats--150 mg/kg. It has a pronounced cumulation ability, cumulation coefficient: Kcum equals 2.9. It has not a local irritant effect on the skin. There were no identified skin-resorptive and sensitizing effects. It causes a slight irritant effect on the mucous membranes of the eyes. It has a toxic effect on the central nervous system, liver, kidneys. Threshold of acute inhalation action is--63.5 mg/m3. Occupational safety level of exposure to sulpiride in the working area air is 0.5 mg/m.

Mechanisms of intracellular defense and activity of free radical oxidation in rat myocardium in the dynamics of chronic fluorine intoxication.

The mechanisms of intracellular defense and activity of free radical oxidation in the myocardium were studied in the dynamics of chronic fluorine intoxication. At the early stages of fluorine intoxication (day 3-week 3), the concentrations of defense proteins HIF-1α, HSC73, and HOx-2 and activity of the main metabolic enzymes increased, which promoted maintenance of cardiomyocyte structure and function at the normal physiological level. At late stages of fluorine intoxication (weeks 6 and 9), metabolic changes in the myocardium attest to high strain of the adaptive mechanisms.

[The experimental search of immunological criteria for identifying stages of development of chronic fluoride intoxication].

The experiment has shown the staging of the development of immune response to the chronic fluoride intoxication. Diagnostic criteria of the initial compensation stage are: leukocytosis against the background of reduced number of lymphocytes and increased one of monocytes; high levels of ceruloplasmin in blood plasma, a progressive increase in TNFalpha and cytokine IL-10. At the decompensation stage there are: leukocytosis with increased number of neutrophils; low levels of ceruloplasmin and the cytokines IL-1beta, IL-4 and the high level of TNFalpha, IL-6, IL-10. At the stage of exhaustion there are: leukopenia against the background of lymphocytosis, a high level of Hp, the low values of the level of IgM, IgG.

[Toxicological characteristic of indole as a basis for its hygienic regulation].

The toxic properties of indole have been studied in terms of LD50 indole was established to refer to moderately hazardous substances: in case of indole introducing into the stomach in rats and mice, DL50 is 1200 mg/kg and 750 mg/kg respectively Indole has a weak ability to cumulation, and has a strong irritant effect to the eyes and a moderate one to the skin. Indole has indiscriminate irritating effect on the respiratory tract: Limir is at Limac (77,8 mg/m3). The occupational exposure of indole in the working area is 1 mg/m3.

[Preclinical study as a basis for hygienic regulation of benzofuran derivatives].

Experiments on laboratory animals studied toxic effects of benzofuran derivatives obtained during anti-arrythmic drug Amiodarone production. Toxic effects were studied for single and subacute intake through intragastric, inhalation and epicutaneous routes. Recommendations are given for hygienic regulation of Amiodarone and intermediate products of its synthesis in the air of workplace.

[Clinical and experimental studies of metabolic response to chronic exposure to coal dust].

In miners anthracosilicosis is caused by chronic exposure to coal dust and is characterized by progressive development of the inflammatory process, the expressed disorders of lipid metabolism, and immunodeficiency. In the experiment we revealed the stages of anthracosilicosis development according to which adequate measures of prevention and correction of the disorders caused by long exposure of an organism to coal dust are recommended.

[Indices of lipid metabolism and peroxidation in normal newborn infants]. / Pokazateli lipidnogo obmena i perekisnogo okisleniia lipidov u zdorovykh novorozhdennykh detei.

Studies of lipid metabolism and peroxidation values, carried out in healthy newborns in the town of Irkutsk, have shown that total lipid and triglyceride levels in these newborns over the first ten days of their lives were similar to those in age-matched infants in the European USSR, whereas plasma total cholesterol levels were significantly higher in them as against the newborns in other regions of the country. The studies included measurements of malonic dialdehyde and total antioxidative activity of blood plasma and red cells, of catalase and peroxidase activities, of red cell peroxidation resistance.

[Lipid peroxidation and the antioxidant system in newborn infants]. / Sostoianie perekisnogo okisleniia lipidov i antiokislitel'noi sistemy u novorozhdennykh.

During measurements of the content of malonic dialdehyde and the total antioxidant activity in blood plasma and red blood cells as well as of their peroxide resistance in healthy neonates, it has been established that in boys and girls the majority of the study parameters did not differ within the first 6 days of life. At the same time in girls, catalase and peroxidase of red blood cells were activated and the total antioxidant activity of blood plasma was increased since the first days after the birth.