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.

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.

[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.

[On theory of sensory conflict under exposure to physical factors: main principles and concepts of formation].

The article presents results of longstanding studies on influence of occupational physical factors on workers health. Experimental and nature studies helped to justify basic concepts of sensory conflict theory, a trigger of occupational disease formation. Patients having occupational disease present disorders of cortex-subcortex relationships on diencephal level, central and peripheral regulatory mechanisms, central sensory mechanisms participation in pathologic processes development, changes in vegetative regulation on cerebral level, demyelination and axon demyelination changes in peripheral nerves of upper and lower limbs. Findings are also changes in central nervous, peripheral nervous systems, endocrine, immune systems, severe emotional negative strain and high level of nervous system excitation, perivascular edema in brain cortex of experimental animals. Based on key principles of the theory, the authors specified and tested new methods of treatment and prevention of occupational diseases caused by physical factors, aimed to unblock the sensory conflict.

[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.

[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.

[Dynamics of morphofunctional state of central nervous system in white rates exposed to vibration].

The authors presented results of experimental studies assessing influence of vibration on white rats. Dynamics of morphologic changes development in brain of experimental animals exposed to vibration were shown. Exposure to vibration in white rats daily during 4 hours over 15 days causes astrogliosis--compensation process in response to brain injury; over 1 month--causes morphologic brain changes (vacuoles formation in neuropile, decrease in astroglia cells number); over 2 months--causes lower plasticity of brain neurons, preserved astrogliosis; over 4 months--causes perivascular edema. Changes in brain bioelectric activity indicate stages of pathologic process in central nervous system. Increase in vibration exposure duration leads to more severe diffuse pathologic changes in brain and local cortical and diencephalic disorders. Exposure to vibration in white rats causes increase in general mobility, nonspecific activation of behaviour, intense emotional exertion, negative emotional state, but less severe effects of vibration were seen in orientative-trying reactions that are inborn, inherited forms of behaviour.

[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.

[Morphologic and neurochemical effects in long-term period of mercurial intoxication (experimental data)].

The article deals with influence of longstanding inhalation of mercurial vapors on behavior of white rats, on morphologic and functional disorders in nervous system, on peculiarities of neuromediators metabolism in brain homogenate over the post-contact period.

[Experimental modelling of toxic encephalopathy].

The article covers problem of experimental biologic modelling of toxic encephalopathies. The authors represent major methodic approaches to modelling, criteria and methods to evaluate pathologic condition of CNS, present results of own research in creating models of toxic encephalopathies caused by metallic mercury and vinylchloride inhalation.

[Morphofunctional disturbances in rats affected vinyl chloride in remote period of intoxication].

Morphofunctional disturbances in rats affected vinyl chloride in remote period of intoxication. The presented data concern influence of inhalation impact of vinyl chloride on nervous system of white rats in remote period.