In Vivo and In Vitro Analysis of Toxicity of a Prospective Magnetic Resonance Contrast Agent Based on Arabinogalactan and Gadolinium Nanocomposite.

We studied the cytotoxic effect of gadolinium nanocomposite on cultured mouse fibroblasts 3T3-SV40 and histological changes in the liver tissue of albino rats after its administration. For in vitro experiment, gadolinium nanocomposite on the natural matrix of arabinogalactan (nGd-AG) was dissolved in DMEM nutrient medium to concentrations of 0.005, 0.02, 0.5, 2, and 5 mM. In in vivo experiment, a nGd-AG solution was orally administered to rats through a tube in a dose of 500 µg Gd/kg in 1 ml of 0.9% NaCl for 10 days. The pattern and degree of influence of the gadolinium nanocomposite on the studied cell culture depended on the concentration and duration of exposure. IC50 of nGd-AG determined after cell incubation for 24, 48, and 72 h were 616 µg/kg (3.9 mM), 302 µg/kg (1.9 mM), and 222 µg/kg (1.4 mM), respectively. Histological changes in the liver of white rats induced by exposure to nanocomposite attested to the development of a compensatory reaction of the organ.

Reproductive Function of Male Rats and Motor Activity of Their Offspring in Fire Emissions Modeling.

We studied the reproductive function of albino male rats after long-term exposure to wildfire smoke and the species-specific behavior of their sexually mature offspring. After the end of exposure, the mean number of spermatogonia and the relative number of Leydig cells in rat testes decreased and the index of spermatogenesis decreased. The offspring of exposed males mated with intact females demonstrated impaired cognitive abilities and disturbances of species-specific behavior. The severity of these changes depended on time interval between the end of the inhalation exposure and mating.

Evaluation of Genotoxicity of Perchlozone, Antituberculous Drug.

Experimental studies of Perchlozone, an antituberculous drug with manifest inhibitory activity towards Mycobacterium tuberculosis and Mycobacterium bovis, were carried out. Genotoxicity of Perchlozone was evaluated by the DNA comet method on liver and lung tissues and blood cells after 14-day inhalation exposure of rats. The level of DNA aberrations in response to inhalations of the drug in a concentration of 102.6±13.7 mg/m3 increased in lung tissue but not in the blood cells or liver. These results indicated genotoxic activity of antituberculous drug Perchlozone.

Contribution of Fetal Programming in the Formation of Cognitive Impairments Induced by Lead Poisoning in White Rats.

The contribution of prenatal hypoxic damage to the CNS to the formation of high sensitivity of the body to lead acetate was studied. Prenatal fetal hypoxia was modeled by the administration of sodium nitrite in doses of 5, 25, and 50 mg/kg to pregnant female rats. Cognitive capacities of mature offspring were evaluated in the radial maze test and Morris water maze test. After attaining learning criterion in the radial maze, lead acetate in a dose of 80 mg/kg was added to the drinking water of all animals over 2 weeks. Testing was performed during the exposure to the agent until disruption of the conditioned behavior. It was found that severe prenatal hypoxia (induced by the administration of 50 mg/kg sodium nitrite) impaired spatial memory, increased latency of funding the platform in Morris water maze test, and serves as a factor contributing to earlier manifestations of the neurotoxic effects of lead acetate.

Experimental lead intoxication symptoms with hyperglycemia state.

In lead intoxication model, with hyperglycenia state, atherogenicity coefficient reached 1,45 (1,35-1,85), if compared to 1,30 (0,85-1,40) in white rats exposed to lead. Heart rate reached 421,00 (411,00-468,00) per minute vs, 385,50 (359,00-399,50) per minute in animals died with lead intoxication, shorter median interval between QRS-complexes up to 143,00 (128,00-146,00) ms vs, 160,00 (150,50-169,00) ms was seen in animals exposed to lead.

Expression of caspase-3 and bcl-2 proteins as an indicator of functional state of brain tissue in white rats exposed to argentumarabinogalactane.

The article presents results on experimental modelling an influence of silver nanoparticles incorporated into natural polymer arabinogalactane matrix on brain tissue of white outbred rats. The rats underwent parenteral injection of silver nanoparticles incorporated into polymer arabinogalactane matrix (dosage of 100 and 500 micrograms of silver per kg of the animal weight). The studies covered expression of 2 proteins participating in apoptosis process, in mitochondrial activation type - caspase-3 and protein bcl-2. During experiment, the groups examined demonstrated significant dose-dependent effect of bcl- 2 protein expression and increased number of caspase-3 expressed and non-expressed hyperchromic cells under exposure to argentumarabinogalactane - that indicates disorders of cellular structure and apoptosis development.

[The study of neurotoxicity of toluene in conditions of experimental modeling of prenatal hypoxic damage of the brain].

There was executed the study of the impact of toluene on indices of behavior, cognitive capabilities and bioelectric activity of the brain in white rats with normal course of the period of antenatal development and against background ofprenatal hemic hypoxia Prenatal hypoxia was modeled in pregnant female rats by subcutaneous injection of sodium nitrite in a dose of 50 mg/kg at from the 10 to the 19 day of gestation. At the age of 3 months the males from the obtained offspring were exposed to inhalation exposure of toluene (150 ppm, 4 weeks). After exposure to toluene in animals there was evaluated the pattern of individual behavior, indices of cognitive capabilities and also bioelectric activity of the brain. There were revealed such common consistencies of transformations in the behavior of exposed to toluene animals with normal and impaired embryogenesis as disturbed motor activity, reduction of exploratory behavior and cognitive functions, impaired bioelectric potentials of the brain. Features of changes in behavior and EEG indices in toluene-exposed rats with prenatal hypoxia are characterized by inhibition of motor activity, increased anxiety and latency of main peaks of auditory and visual evoked potentials. Prenatal hypoxic damage of the central nervous system was shown to be an aggravating factor in toluene intoxication in rats.

[Induction of apoptosis in neurons of white rats under exposure of nanobiocomposite based on ag (0) nanoparticles and arabinogalactan].

There are presented results of the immunohistochemical study of neural tissue of outbred albino rats exposed for 9 days to the influence of the silver nanobiocomposite consisted of silver nanoparticles encapsulated into a matrix of a natural polymer - arabinogalactan. The research of albino rats was performed in 2 stages: half of the rats in each groups were decapitated immediately after the exposure (early period) and the rest animals - 6 months after the end of exposure (remote period). The impact of the studied substance was proved to cause functional changes in cells of the nervous tissue. After the subacute administration of the nanobiocomposite - argentum-arabinogalactan (nano-Ag-AG) in cells of the nervous tissue of the brain of albino rats the expression of apoptotic and anti-apoptotic protein (caspase-3 and bcl-2) was established to be changed. The number of normal neurons producing protein caspase-3 sharply increases. Herewith the number of immunonegative neurons fairly declines. Along with this there is noted the high level of bcl-2 content, one function ofwhich is the preclusion ofapoptosis. In preparations there is revealed a significant gain in the number of bcl-2 expressing neurons, however, the protective effect of the protein is not fully realized, that leads to the significantly increase in the content of damaged hyperchromatic cells. The evaluation of results of the immunohistochemical study of the nervous tissue of albino rats according to data concerning the proteins caspase-3 and bcl-2 expression permits to make a conclusion about the capability of nanoargentum encapsulated into polymer matrix by passing the blood-brain barrier to induce the triggering apoptosis cascade in neurons of the cerebral cortex.

[Alteration of white rats brain tissue inducted by assessment of silver nanocomposite incapsulated in polymer matrix].

The paper present experimental materials of intragastric administration of silver nanoparticles encapsulated in polymer matrix of arabinogalactan by white outbred male rats. Animals were injected "pure" arabinogalactan and colloid silver solution containing silver macroform separately for comparison. Research provided data about status of brain tissue at the impact of these substances on organism. Histological analysis revealed the presence of a pathological process, character and intensity of which varied depending on the type of injected material. Pathological process under the influence of silver-arabinogalactan characterized by appearance in brain tissue of perivascular edema and development of acute inflammation in formation of glial scars, swelling of vascular bundles in sum.

[Evaluation of biologic effects caused by nano-silver influence on brain tissue of experimental animals].

The article presents results of histologic and immunohistochemical examination of nerve tissue of outbred white rats subjected over 9 days to nanobiocomposite containing nanoparticles of silver and natural biopolymer arabinogalactane. Exposure to the studied chemical was proved to cause structural and functional changes in nervous tissue. Comparing results of structural study of nervous tissue with expression of proteins caspase-3 and bcl-2 proves ability of nanosilver incapsulated into polymer matrix to penetrate through blood-brain barrier and induce apoptosis in neurons of brain cortex.

[Methodological approaches to the experimental study of the impact of environmental pollution on the human body].

In the materials there are presented features of methodological approaches in the performing of experimental studies concerning of the investigation of the impacts of environmental factors on the human body. There were shown the results of our experiments performed at the Institute, in the modeling of biological effects of antimicrobial nanobiocomposites with nanosilver particles, toxic encephalopathy, in the study of the combined effect of the factors of biological and chemical nature. There was proved the importance of intracellular of proteomics in the assessment of the effects of the action of nanoparticles and nanomaterials on the body. There were revealed key parts of progredient course of mercury poisoning in the long-term. The special section is presented by the study of long-term effects of anthropogenic environmental factors on subsequent generations. There are presented results witnessing to a deterioration of the functional state of the central nervous system in rats in the first and second generations, whose parents were exposed to neurotoxicants. There was proved the aggravating role of prenatal hypoxia in the development of toxicity in rats in sexually mature age. Experimental biomodeling is aimed at sighting of pathogenetically substantiated treatment and preventive measures: initially, in experimental conditions, and in the future in the rehabilitation of sick or injured patients.

[Neurotoxic effect of toluene on background of prenatal hypoxic brain damage to white rats].

Comparative study covered influence of toluene on behavioral parameters, cognitive abilities and brain bioelectric activity in white rats with normal embryonic development or with prenatal hypoxia. Prenatal hypoxia was simulated by subcutaneous injection of 50 mg/kg sodium nitrite into female white rats on day 13-14 of gestation. The offspring at the age of 2, 5-3 months was exposed to toluene (concentration of 560 mg/m3, 4 hours per day, 5 days per week, over 4 weeks). After the exposure, the animals were estimated for individual and intraspecific behaviour in "open fields and "resident-intruder" tests, for cognitive abilities in "radial maze" training, EEG with visual and auditory evoked potentials. Acute hypoxia at early stages of organogenesis appeared to be burdening factor and to influence consequences of toluene intoxication.

[Occupational neurointoxications: patterns and mechanisms of formation].

The article covers results of long-standing study of clinical features of occupational neurointoxications in late period, and mechanisms underlying nervous system disorders in individuals working under long exposure to neurotoxic chemicals and in late period of occupational intoxications. With modern neurophysiologic, neuropsychologic, immunologic and biochemical diagnostic methods, the authors specified early manifestations of occupational disorders. Translation patterns of neurointoxications are specified.

[Improving methodical approaches to experimental studies in the field of occupational medicine].

The features of the methodical approaches in performing the experimental studies dealing with studying the working condition and the health state in the employees are presented in this paper. The results of our experiments performed in the Institute based on modeling the occupational toxic encephalopathy, studying the combined factor activity of the biological and chemical nature developing the methodical approaches to the assessment of the biological activity effects of the nanomaterials are indicated. The purposefulness of performing the experiments in the occupational medicine using the non-breedy and line-breedy animals is considered.

[Evaluation of the biological effects of chemical substances on albino rat offspring].

The paper provides the results of experimental studies of the impact of vinyl chloride or sublimate intoxication in male albino rats on the functional state of the nervous system of their offspring. Retarded sensorimotor development was revealed in the neonatal offspring. The pubertal offspring showed behavioral pattern disintegrity that was characterized by changes in motor activity and orientative-exploratory responses and by anxiety. There was abnormal impulse conduction in the neuromuscular apparatus of the hind legs of albino rats and morphological changes in the structure of nervous tissue.

[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.

[Biomodelling for environmental factors influence on humans].

The article covers results of experimental modelling under exposure to biologic factor associated with chemical factor, and neurotoxic process caused by injection of vinylchloride, inorganic mercury compounds and toxic chemical complex. The authors specified methodologic approaches to evaluate and forecast character of biologic effects in laboratory animals response to influence of environmental factors.

[Risk assessment of combined exposure to environmental biological and chemical factors on man].

The paper provides the results of experimental risk assessment of exposure to a biological factor combined with a chemical factor, which present with the protein-bearing dust and sulfur dioxide. The regularities and specific features of the functioning of the body's physiological systems have been revealed in the development of responses to combined exposure to biological and chemical factors, which show that the response may take three basic paths: sensitization, allergopathy, and toxic allergopathy. The essentials of the methodology evaluating and predicting the nature of the biological effects of a response in the experimental study of combined exposure to biological and chemical factors of the nature have been developed.

[Toxic encephalopathies in distant post-contact period of occupational neurointoxications (clinical and experimental studies)].

The article covers results of long-standing research on clinical peculiarities and course of toxic encephalopathy in distant period of occupational neurointoxications, on main concepts and pathogenetic steps of formation and progress of toxic encephalopathy. Through investigation covered firemen after exposure to complex of toxic chemicals and patients in post-contact period of chronic mercury intoxication. Modelling of chronic inhalation of metallic mercury vapors was performed.

[Disturbance of the microenvironment of upper respiratory tract mucosa as an indicator of early changes in the health status under combined effect of toxic substances].

Results of quantitative and qualitative assessment of mucosal microbiocenoses in the upper respiratory tracts are presented along with cytomorphological characteristics of upper airway mucosa. SIgA and lysozyme concentrations were measured in the saliva of firemen. Their exposure to occupational hazards during periods of professional activity was shown to lead to a decrease in non-specific anti-infectious resistance to the effect of unfavourable factors.