Cadmium compounds are highly toxic substances characterized by mutagenic, genotoxic and carcinogenic effects, and having high cumulative properties. Application of cadmium nanoparticles (NPs) in medicine stimulates the study of their mechanism of action at the cellular level and at the level of organs and systems, determination of biomarkers of their action, particularly in comparison with the ionic form. The aim of the study was to compare the features of cytotoxic and genotoxic effects of cadmium sulfide (CdS) NPs of different sizes on cell cultures of different histogenesis with those of cadmium chloride (CdCl2). Materials and Methods: In this work, we used cadmium compounds in the nanoform: NPs CdS of 4–6 nm and of 9–11 nm in size; and in the ionic form: CdCl2. The studies were conducted in vitro in cell lines — IMR-32, НEК-293 and MАEC. To count viable cells we compared the results of three basic tests: MTT (methyl tetrasolium test), SRB (sulforhodamine B test) and NRU (neutral red uptake test). We evaluated the genotoxic effect of the substances studied in vitro using DNA comet assay in alkaline conditions. Results: CdS NPs and CdCl2 demonstrated pronounced dose-dependent cytotoxic effect in MАEC, НEК-293 and IMR-32 cell lines, by impairing membrane permeability, functioning of mitochondria and lysosomes, and inhibiting the function of protein synthesis. Cytotoxic effect of CdCl2 was the most pronounced, this effect of CdS NPs of 9–11 nm in size being the least pronounced. The comet DNA assay in alkaline conditions revealed a statistically significant increase in DNA comet index when exposed to CdCl2 and CdS NPs in comparison with the negative control, which indicates their genotoxic effect. CdS NPs of 4–6 nm in size showed a more pronounced effect in comparison with those of 9–11 nm in size. Conclusion: Elucidation of mechanisms underlying the implementation of toxic effects of cadmium NPs will help in assessing the potential risks associated with their use in industry and developing effective preventive measures. For instance, when planning in vivo studies for toxicological evaluation of nanomaterials and nano-substances containing NPs of cadmium, it is necessary to investigate the mutagenic and carcinogenic risks and to take into account the high likelihood of neurotoxic and cardiovasotoxic effects, along with nephrotoxic effects, since high cytotoxic activity of the investigated compounds of cadmium was detected on the cells of the MАEC line (endothelial origin) and IMR-32 (neuronal origin).

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Introduction of nanotechnologies to the modern industry gave rise to new challenges. The issue of development and implementation of recommendations regarding the prevention of potential negative impact of lead nanoparticles on population health is of particular importance. The locally manufactured drug Thiocetam which possesses nootropic, antiischemic, antioxidative and membrane stabilizing properties has drawn our attention. The research aimed at studying the protective effect of Thiocetam in Wistar rats with simulated subchronic toxic effect of lead compounds of various sizes (by morphological changes in the heart and vessels). The experiments were conducted on Wistar rats (mean body weight of 160-180 g). Colloidal solutions of lead sulphide obtained by chemical synthesis with the use of sodium polyphosphate stabilizer, (PbS) with the mean size of 26-34 nm (1-PbS) and 50-80 nm (2-PbS), and lead nitrate Pb(NO3)2 (3-Pb) in the ionic form were used in simulating the toxic effect, while normal saline solution was administered to the control group. The studied substances were injected (intraperitoneally daily 5 times a week) in a dose of 0.94 mg/kg (in lead equivalent). The toxic effects were evaluated after 60 injections (three months) and one month after the discontinuation of exposure with and without Thiocetam. The drug Thiocetam in the dose of 250 mg/kg had been administered to rats intragastrically on an empty stomach daily for one month. Histological slides of the rats’ myocardium and aortal wall were studied and morphometric analysis and statistical processing performed. In the postexposure recovery period (PEP) period a lower degree of interstitial swelling and myocardial blood vessel filling was observed, which was considered to be a regression of damage. After the administration of Thiocetam a pronounced transverse striation of cardiomyocytes, the density of collagen fibers around cardiomyocytes and microvessels were revealed, which indicated the protective effect of pharmacological correction. However, leukocyte infiltration was also found in the myocardial or aortic microvessels in the experimental groups. Aortic morphometric data revealed no differences between the PbS NPs groups and Pb(NO3)2, although the aortic wall morphology was quite preserved. The use of Thiocetam prevented dystrophic changes in the atrial epicardium and the aortic adventitia, which indicate cytoprotective and connective tissue effects. In the postexposure period without pharmacological correction a tendency to spontaneous recovery of morphological changes of the heart and aortic walls under the influence of PbS NPs and lead nitrate was observed. However, morphometric parameters demonstrate the absence of complete recovery be it with or without Thiocetam.

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ДУ «Інститут медицини праці НАМН України» лабораторія промислової токсикології та гігієни праці при використанні хімічних речовин (зав. -д. мед. н., проф., член-кор. НАН України, академік НАМН України І.М. Трахтенберг) вул. Саксаганського, 75, Київ, 01033, Україна SI «Institute for Occupational Health of AMS of Ukraine» laboratory of industrial toxicology and occupational hygiene when using chemicals Saksaganskogo str., 75, Kyiv, Ukraine e-mail: ol_apyht@ukr.net Ключові слова: наночастинки, кадмій, токсичність, вміст у внутрішніх органах. Key words: nanoparticles, cadmium, toxicity, content in internal organs Реферат. Динамика накопления кадмия во внутренних органах крыс после длительного введения хлорида кадмия и наночастиц сульфида кадмия разных размеров. Апыхтина Е.Л., Козлов К.П. В статье представлены результаты исследования особенностей накопления кадмия во внутренних органах крыс линии Вистар после длительного внутрибрюшинного введения хлорида кадмия и наночастиц сульфида кадмия размером 4-6 нм и 9-11 нм в дозе 0,08 мг/кг/сутки в пересчете на кадмий. Токсические эффекты оценивали после 30 введений (1,5 месяца), 60 введений (3 месяца) и через 1,5 месяца после прекращения экспозиции. Результаты исследования показали, что наиболее интенсивное накопление кадмия наблюдалось в почках и печени экспериментальных животных, что обусловлено как особенностями токсикокинетики, так и путем введения исследуемых соединений в организм. В почках, селезенке и тимусе животных, экспонированных наночастицами сульфида кадмия, было обнаружено большую концентрацию кадмия по сравнению с органами животных, которым вводили хлорид кадмия. Причем в селезенке более интенсивно накапливался кадмий после введения наночастиц большего размера по сравнению с почками и тимусом. В печени, сердце, аорте и головном мозге животных значительное накопление наблюдалось после введения хлорида кадмия.Abstract. Dynamics of cadmium acclumulation in the internal organs of rats after exposure to cadmium chloride and cadmium sulphide nanopartiles of various sizes. Apykhtina O.L., Kozlov K.P. The article presents the results of study of cadmium accumulation in the internal organs of Wistar rats after prolonged intraperitoneal administration of cadmium chloride and cadmium sulphide nanoparticles of 4-6 nm and 9-11 nm in size in a dose of 0.08 mg /kg/day calculated as cadmium. Toxic effects were evaluated after 30 injections (1.5 months), 60 injections (3 months), and 1.5 months after the exposure has been ceased. The results of the study showed that the most intensive accumulation of cadmium was observed in the kidneys and liver of experimental animals, which is due to the peculiarities of the toxicokinetics and the route of administration of cadmium compounds. In the kidneys, spleen and thymus of animals exposed to cadmium sulphide nanoparticles, a greater concentration of cadmium than in the organs of animals exposed to cadmium chloride was found. Cadmium accumulated more intensively in the spleen after exposure to larger nanoparticles, than in the kidneys ...