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.

No more than 100 nm large, nanoparticles (NPs) are distinguished by unusual mechanical, electrical, optical, thermal and magnetic properties. They are used in biology, pharmacology, medicine, chemistry, physics, materials technology and engineering industry. Nanoparticles penetrate in organism through the skin, GIT and airways. Their genotoxicity depends on size, form, mode of action and composition. Two principal mechanisms of NPs genotoxicity are primary and secondary. The primary mechanism is realized in direct interaction with the genome; the secondary mechanism is achieved through mediation of the active forms of oxygen. NPs can modulate the epigenome by altering the gene functions and do not change the DNA sequence directly. Consequences of prolonged exposure to low NPs doses on the human organism still remain uninvestigated.

An analysis of the acute and subacute toxicity of a copper oxide nanocomposite (NC) encapsulated in natural polymeric matrix of arabinogalactan is presented. The study was carried out in two stages. At the first stage, the acute toxicity of the NC was studied. For this, white mice were orally administered one time with an aqueous solution of NC at a dose 2000 mg/kg. The study demonstrated that according to this parameter, NC belongs to low-toxicity substances of hazard class 5. At the second stage, the biological response of the white rats was evaluated with a subacute intragastric effect of Cu2ОAG NC at a dose of 500 µg/kg (based on Cu) body weight within 10 days. The study demonstrated an increase in the contents of copper in the brain tissue, liver, and kidneys compared with the control group. Morphological and neurophysiological changes were detected in white rats treated with this NC. A pronounced macrophage reaction consisting in an increase in the number of Kupffer cells in the organ sinusoids was observed in liver tissue. In the tissues of the sensorimotor cortex of the brain, a sharp decrease in the number of astroglia cells was detected, which indicates a selective cytotoxicity of this NC. When studying the bioelectric activity of the sensorimotor cortex of the brain in animals a decrease in β-2 rhythm of background electroencephalogram, as well as a decrease in the amplitude of the P2 and N2-P3 peaks of the visually evoked potentials, were observed. No genotoxic effects were detected under the influence of the NC.

Introduction. The article presents a toxicity analysis of the Fe3O4 nanocomposite encapsulated in the natural polymer matrix of arabinogalactan (AG). A study was devoted to forming and developing the biological response of organisms to subacute administration of this nanocomposite. Materials and methods. White outbred male rats weighing 200-220 gr. were used in this study. For ten days, a test drug solution was administered orally to animals with a probe at a dose of 500 μg of iron per kilogram of body weight. Then, using histological and immunohistochemical analysis methods, the severity of the biological response of the organism to the introduction of this nanocomposite was evaluated. An analysis was made of the state of tissue of the liver, kidneys, and sensorimotor cortex. The number of neurons with the proapoptotic caspase three protein expression, anti-apoptotic bcl-2 protein, and HSP 70 stress protein was determined in the sensorimotor cortex tissue. Results. With intragastric administration to experimental animals, there was a violation of normal blood rheology in liver and kidney tissue, protein dystrophy of hepatocytes, expansion of perivascular spaces of brain tissue, and a decrease in the total number of sensorimotor cortex neurons per unit area. Immunohistochemical analysis of tissue of the sensorimotor cortex for expression of pro-and anti-apoptotic proteins and the expression of HSP 70 protein showed a sharp increase in the number of neurons with the expression of HSP 70 stress protein. Discussion. The nature of the detected changes indicates the occurrence of compensatory-adaptive reactions in the organism in response to the effect of FeAG. The lack of expression of caspase 3 protein eliminates the development of apoptosis.

Relevance. Metals are transported by run-off from human settlements and industrial plants and accumulate in the sediments of water bodies. Lead is found in high concentrations in the soil of agricultural land. Lead can be transported with water, seafood, animal products and plants to humans. Poisoning may occur in workers and in the population in contact with lead. At the same time, hypothyroidism is a widespread disease, often due to living in areas of endemic iodine deficiency in water and soil. Latent hypothyroidism can aggravate occupational effects of heavy metals in exposed workers.Intention. To study behavioural and morphological changes in rats with lead poisoning aggravated by medicinal hypothyroidism. Methodology. 32 albino outbred adult male rats were studied. Lead poisoning was induced by lead acetate at a dose of 60 mg/kg body weight in drinking water tanks for 30 days. Hypothyroidism in rats was induced from the ninth day of the experiment with daily injections of thyrozol (thyroid static substance) at a dose of 30 mg/kg for 21 days. Behavioral responses in rats were studied using open field tests, and survey records were processed using Real Timer. For morphological analysis, layered serial cuts of brain tissue were prepared and painted using the Nissl method, and slides were visualized via observation microscopy.Results and Discussion. Under lead poisoning, animals demonstrated decreased locomotor and exploration activity and increased anxiety with increasing intoxication combined with hypothyroidism. Changes in the rat brain after exposure to lead were confirmed histologically: increased neuron degeneration, neuronophagia and glyosis. New histological data were obtained in case of lead-thyrozol combination: increased neuronal death, decreased number of astroglial cells compared to animals exposed to lead only. This suggests predominant irreversible neurodegeneration due to combined effects of lead poisoning and thyroidstatic exposure.Conclusion. Under combined exposure to lead and tyrozol, the thyroidstatic substance exacerbated decline in locomotor and exploration activity as well as lead-associated neurodegenerative processes in the rat brain.

Introduction. Due to their high biocompatibility, substances based on nanosized selenium particles, encapsulated in natural or synthetic polymer matrices, are promising materials for the creation of biomedical preparations of diagnostic and therapeutic value. Selenium nanoparticles are successfully used in the diagnosis of various types of cancer. In addition to the diagnostic value, selenium nanoparticles have their own prophylactic and oncological effect. This paper presents the results of a study of the toxicity of the Se nanocomposite encapsulated in the polymer matrix of arabinogalactan (SeAG). The emergence and development of the pathological process in the tissue of the brain, liver and kidneys during subacute administration of this nanocomposite was studied.Materials and methods. Twenty white outbred male rats weighing 200–220 g were used in the work. Animals were orally administered a solution of the selenium nanocomposite at a dose of 500 μg per kilogram of animal body weight for 10 days. Then, using the methods of histological analysis, the severity of the biological response of the organism to the introduction of this nanocomposite was assessed. An analysis of the state of the tissue of the liver, kidneys and the sensorimotor cortex of the brain was carried out.Results. With the intragastric administration of this drug, there is stasis of blood in the portal tracts, a pronounced macrophage reaction and diapedesis of leukocytes in the liver tissue. There is a decrease in the number of normal neurons per unit area, a decrease in the number of astroglia cells and an increase in the number of degeneratively altered neurons in the tissue of the sensorimotor cortex. There is also an increase in connective tissue in the cortex of the kidney, with the formation of fibrosis and a decrease in the area of the Shumlyansky – Bowman capsule.Conclusion. The effect of the investigated nanocomposite is characterized by the development of a pronounced pathological process in the central nervous and hepatorenal systems of the body.

The results of a study on rats toxicity of nanoparticles of metals bismuth, gadolinium and silver encapsulated in a natural biopolymer matrix arabinogalactan are presented. When intake of nanocomposite of silver revealed the readiness of the brain cell to apoptosis. The effect of bismuth and gadolinium nanocomposites did not cause an increase in the process of programmed cell death.

Представлены результаты исследования биобезопасности двух нанокомпозитов гадолиния, инкапсулированных в природную полимерную матрицу арабиногалактана, и дана сравнительная оценка их токсичности. Для этого белым беспородным крысам-самцам внутрижелудочно с помощью зонда вводили раствор исследуемых нанокомпозитов в дозе 500 мкг гадолиния на килограмм массы тела животного. Методами гистологического и иммуногистохимического анализа оценивали выраженность биологического ответа организма на введение данных нанокомпозитов. Оценивали состояние ткани печени и сенсомоторной коры головного мозга. В ткани головного мозга определено число нейронов с экспрессией проапоптотического белка каспаза 3, антиапоптотического белка bcl-2 и стресс-белка БТШ 70. Определены общие точки приложения патологического процесса при воздействии исследуемых нанокомпозитов и индивидуальные особенности формирования патологического процесса для каждого нанокомпозита.

Introduction. In recent years, magnetic nanoparticles, which can simultaneously have a therapeutic effect on the pathological focus, are used to magnify contrast enhancement and increase diagnostic sensitivity during magnetic resonance therapy (MRT). The last is carried out by the effective capture of neutrons, which among all the chemical elements is most pronounced in gadolinium. The use of gadolinium nanoparticles encapsulated in a polymeric matrix allows increasing the bioavailability of nanoparticles, reduces the possible toxicity of drugs. Aim. Evaluation of impact of new nanocomposite magnetically active metal complex gadolinium system on the morphofunctional state of the nervous tissue, liver, and kidney of rats. Material and methods. Experimental studies of biological effects of gadolinium-arabinogalactan nanocomposite (Gd-AG) were carried out on rats that were injected intraperitoneally for 10 days at the dose of 500 μg/kg in 0.5 ml of saline. Animals were sacrificed by decapitation under light ether anesthesia the next day after the end of exposure. To perform pathological studies, frontal sections of the temporal-parietal zone of the sensorimotor cortex, liver and kidney tissues were stained on ordinary histological glass slides with hematoxylin and eosin for viewing microscopic picture. The immunohistochemical method was used to determine the activity of the bcl-2, caspase-3 and hsp70 modulatory protein in apoptosis of white rats in brain neurons and to study the biological response of the organism at the subcellular level. Results. Histological analysis of tissues revealed a pronounced compensatory response of liver, a violation of the functional activity of kidneys. A decrease in the total number of normal neurons per unit area in brain tissue and an increase in the number of acts of neuronophagy indicate the initial stage of neurodegenerative process. Evaluation of the intracellular metabolism of neurons has not established the presence of signs characteristic of apoptotic process. Conclusion. The subacute effect of Gd-AG in a dose of 500 µg/kg causes a disturbance of morphofunctional state of liver, kidneys and nervous tissue, as well as modulation of cellular proteomics.

Background. The creation and the attempt to introduce into medicine new nanostructured materials dictate the need for careful study of their safety for human health and the environment. At the same time, the existing classical approaches to safety assessment do not always objectively reflect the real state of affairs; therefore, there is a need to introduce new approaches, including methods of intracellular safety assessment of nanoparticles and nanomaterials.The aim of this study was to evaluate expression level of apoptosis-regular proteins caspase-3 and bcl-2 in neurons of white outbred rats exposed to nanocomposites consisting of nanoparticles of metals (silver, bismuth and gadolinium) on a natural matrix of arabinogalactan isolated from Siberian larch wood.Materials and methods. Sixty outbred male rats were exposed to nanocomposites for 9 days at a dose of 500 μg of metal per 1 kg of animal body weight. The introduction of substances was carried out orally using atraumatic probe. Study of the activity of proteins of apoptosis modulators caspase-3 and bcl-2 and calculate the percentage of different types of reacted neurons was conducted. Statistics 6.1 was used to process results, p-values less than 0.01 were acknowledged as statistically significant.Results. It was found that the activation of apoptotic process occurs only when the nanocomposite is affected with the addition of silver nanoparticles, which are realized in a significant increase in the percentage of all types of neurons under study.Conclusion. Monitoring proteins – regulators of apoptosis can serve as a marker of early damage to nerve cells, since glial cells can form at the site of dead neurons that do not fulfill the main function of transmission of nerve impulses. The results obtained allow us to substantiate the need for a more thorough and prolonged study of silver nanoparticles encapsulated on the arabinogalactan matrix.

The aim was to assess the effect of silver nanoparticles on the expression of proand anti-apoptotic proteins caspase-3 and bcl-2 by discriminant analysis.Materials and methods. 120 sexually mature outbred male rats were divided into 8 groups (pure arabinogalactan (AG), pure poly-1-vinyl-1,2,4-triazol (PVT), nanobiocomposites on the AG and PVT matrix at a dose of 100 and 500 μg/kg. The administration was done orally for 9 days. The experimental study was carried out in two stages. The first stage included the examination of animals immediately after the end of the exposure of the studied substances (early period), the second stage – a survey 6 months after the end of the exposure (the long-term period).Results. The most distinguished groups were the groups that were administered silver nanoparticles on the AG matrix at a dose of 100 and 500 μg/kg.Conclusion. Comparison of the results of the discriminant analysis allowed to fully determine the effect of silver nanoparticles on the expression of proand anti-apoptotic proteins caspase-3 and bcl-2 when they were introduced on the AG and PVT matrix. In the AG groups and nanobiocomposites based on it, in the feature space, it was shown that the most remote by differentiating characteristics are the groups nAG100 and nAG500. In nanocomposites on the PVT matrix, a group of animals differing in differentiating features has not been identified.

Introduction. Experimental studies in animals have shown ultrastructural changes in hepatic sinusoidal endothelial cells, tissue hypoxia of the kidneys, changes in the activity of oxidative processes and antioxidant enzymes, the formation of bioenergetic hypoxia, cell response in the form of infiltration of both lymphoid and macrophage cells to develop due to exposure to vibration. However, there is almost no data about the status of animals’ organs in the post-contact period. Material and methods. The study was carried out in white male rats weighing 220-240 g, were exposed to 40 Hz vibration for 60 days 5 times a week for 4 hours a day. Histological and morphometric analysis was used to assess the sensorimotor cortex tissue and hepatorenal system. Results. A decrease in the total number of brain neurons, astraglial cells in rats in 30, 60 and 120 days of the post-exposure period was found. There was hyperemia in the portal and Central veins, an increase in the number of Kupffer cells in the liver tissue at the 30th, 60th, 120th day after the exposure. Decrease in the area of the Shumlyansky-Bowman capsule was recorded in the experimental rats’ kidney tissue 30 days after the end of vibration exposure; though there were no differences in the number of renal bodies in the tissue of white rats of the experimental and control groups at 60th and 120th day after the end of exposure to vibration. Conclusion. Morphological changes in the tissues of white rats exposed to prolonged vibration presented in the form of a decrease in the total number of neurons and astroglia cells in the brain tissue, a pronounced macrophage response in the liver tissue have been preserved in the post-contact period following the exposure to vibration.

The aim was to assess the effect of silver nanoparticles on the expression of proand anti-apoptotic proteins caspase-3 and bcl-2 by discriminant analysis. Materials and methods. 120 sexually mature outbred male rats were divided into 8 groups (pure arabinogalactan (AG), pure poly-1-vinyl-1,2,4-triazol (PVT), nanobiocomposites on the AG and PVT matrix at a dose of 100 and 500 μ g/kg. The administration was done orally for 9 days. The experimental study was carried out in two stages. The first stage included the examination of animals immediately after the end of the exposure of the studied substances (early period), the second stage – a survey 6 months after the end of the exposure (the long-term period). Results. The most distinguished groups were the groups that were administered silver nanoparticles on the AG matrix at a dose of 100 and 500 μ g/kg. Conclusion. Comparison of the results of the discriminant analysis allowed to fully determine the effect of silver nanoparticles on the expression of proand anti-apoptotic proteins caspase-3 and bcl-2 when they were introduced on the AG and PVT matrix. In the AG groups and nanobiocomposites based on it, in the feature space, it was shown that the most remote by differentiating characteristics are the groups nAG100 and nAG500. In nanocomposites on the PVT matrix, a group of animals differing in differentiating features has not been identified.

Abstract—The article presents theresults of a biosafety study of two gadolinium nanocomposites encapsulated in the natural polymer matrix of arabinogalactan and gives a comparative assessment of their toxicity. A probe was used to administer per os white outbred male rats with a solution of the studied nanocomposites in a dose of 500 μg gadolinium per kilogram of animal body weight. Histological and immunohistochemical analysis was applied to assay the severity of an organism’s biological response to these introduced nanocomposites. The state of liver tissue and the sensorimotor cortex were evaluated. In brain tissue, the number of neurons with expression of proapoptotic caspase 3 protein, antiapoptotic bcl-2 protein, and HSP stress protein 70 were determined. The authors determined the general points of application of the pathological process under the action of the studied nanocomposites and individual features of formation of the pathological process for each nanocomposite.

The synthesis of a water-soluble polymer nanocomposite with Ag(0) particles encapsulated in a poly(1-vinyl-1,2,4-triazole) matrix is reported. The nanocomposite contains isolated spherical Ag(0) particles sized from 2 to 8 nm that are uniformly distributed in the polymer matrix and have a characteristic plasmonic absorption maximum at 412 nm. The new nanocomposite belongs to marginally hazardous category 4. The structural morphology of animal brain tissue is not disturbed after subacute intragastric injection. The bacteriostatic concentration of the nanocomposite varies in the range 0.5 – 32 μg/mL; bactericidal, 1 – 64 μg/mL.

В материалах описан процесс синтеза нанокомпозитов селена и теллура на полимерной матрице — арабиногалактан. Представлена детализация их физико-химических и биологических свойств. Исследования параметров острой токсичности и половой чувствительности к нанокомпозиту селена с арабиногалактаном показали: при остром внутрижелудочном пути поступления нанокомпозит характеризуется как вещество, имеющее низкую опасность острой токсичности, отсутствуют различия в половой чувствительности животных. При исследовании биологических свойств нанокомпозитов Te и Se с арабиногалактаном изучены концентрационные зависимости цитотоксичности композитов для клеток культур человека HEp-2 и ECV-304, а также фибробластов почки зеленой мартышки (Vero B). Установлено, что нанокомпозиты Te и Se демонстрировали у всех исследованных культур разную зависимость цитотоксичности от концентрации. Показано, что нанокомпозит арабиногалактана с элементным селеном обладает бактерицидным эффектом по отношению к возбудителю кольцевой гнили картофеля Clavibacter michiganensis subsp. sepedonicus.

This paper reports the synthesis of nanocomposites of selenium and tellurium on a polymer matrix: arabinogalactan. Their physicochemical and biological properties are presented in detail. Studies of the parameters of acute toxicity and sex sensitivity to the nanocomposite of selenium and arabinogalactan show the following. The nanocomposite is characterized as a substance with a low acute toxicity hazard in the acute intragastric route of entry; no differences in the sex sensitivity of animals are revealed. The concentration dependences of the cytotoxicity of composites for human HEp-2 and ECV-304 cell cultures, as well as the green monkey kidney fibroblasts (Vero B), are studied during the investigation of biological properties of the nanocomposites of Te and Se with arabinogalactan. It is found that the Te and Se nanocomposites exhibit a different dependence of cytotoxicity on the concentration in all cultures studied. The nanocomposite of arabinogalactan with elemental selenium is shown to have a bactericidal effect against the causative agent of the ring rot of potato Clavibacter michiganensis subsp. sepedonicus.

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.

A new functional water-soluble copolymer and its silver-containing nanocomposite have been synthesized by radical copolymerization of 1-vinyl-1,2,4-triazole with N-vinylpyrrolidone. The silver content in the nanocomposite is 8.0% (atomic absorption spectroscopy data). The presence of nanosized metal phase was confirmed by UV spectroscopy and transmission electron microscopy. Dimensions of silver nanoparticles range from 1 to 8 nm. The toxicity studies of the synthesized copolymer and the silver nanocomposite have shown that upon intragastric introducing to white mice its lethal dose (LD50) is more than 5.000 mgxkg(-1). Macroscopic study of animal organ tissues does not reveal any structural changes.