Page 79 - Zbornik_Konf_2019

https://doi.org/10.15414/2019.9788055220703

4 International Scientific Conference Abstracts Book
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THE SAFETY ASSESSMENT OF INNOVATIVE DRUGS OF MICROELEMENTS RECEIVED BY
NANOTECHNOLOGY
Nataliia Dmytrukha, Tamara Korolenko, Olha Lahutina, Liudmyla Lehkostup

State Institution “Kundiev Institute for Occupational Health of National Academy of Medical Sciences of
Ukraine”, Kyiv, Ukraine; E-mail.: dmytrukha@ukr.net
Modern nanotechnology offers broad prospects for the production and use of metals-
microelements in the new form of nanoparticles. High permeability and bioavailability of
metals nanoparticles make them a valuable product for the creation of innovative mineral
fertilizers for agricultural plants. However, the lack of knowledge about their possible danger
to human health and the environment determines the need for toxicological studies. The aim
of this study was to evaluate the toxicity of citrates of metals (Fe, Cu, Zn, Mg) received by
nanotechnology on the human cells culture and blood plasma proteins in vitro.
The citrates of metals obtained using the nanotechnology method developed by
Kaplunenko-Kosinov. The cyto- and genotoxic effects of metals citrates were investigated on
the culture of lung cancer cells (line A-549) and normal keratinocytes (line HaCat) using well-
known methods MTT-test and micronucleus test. Conformational changes f human blood
plasma proteins (albumin, immunoglobulin G) were determined by normal
spectrophotometer and MALDI-tof mass spectrometer. The statistical validity of the obtained
results was evaluated according to the Student's criterion.
It was found that incubation of cells with high concentrations (2 mg/ml) of metal
citrates caused cells death. The highest cytotoxic activity on the cells A-549 and HaCat showed
citrates of Cu and Zn. But Fe citrate causing a cytotoxic effect of about 10 times less than Cu
citrate. The smallest toxic effect on the cells of both lines was established for Mg citrate. The
concentrations of metal citrates (Fe – 0.025 mg/ml, Mg – 1.00 mg/ml, Zn – 0.005 mg/ml, Cu –
0.002 mg/ml) were harmfully influenced the stability of the cells chromosomes. The greatest
genotoxic effect was caused by Zn and Cu citrates, they also the most inhibited cell
proliferation. Zn, Cu and Mg citrates caused increased frequency of dual-core cells, that
affected the structure of the cytoskeleton and spindle division. Under the influence of these
metals citrates, the rate of cell division was slowed down (judging by the change in the ratio of
the number of mitoses and dual-core cells per 1000 cells). The incubation of human albumin
and immunoglobulin with metals citrates in vitro caused changes of experimental protein
solution optical density and protein masse. These data indicate changes in the structure of
proteins, including their denaturation. The major changes in the structure of the proteins
caused Fe citrate and the smallest – citrates of Zn and Mg. The obtained results suggest that
the cytotoxic and protein denaturing activity of the nanotechnological metals citrates
depended on the toxicity of the metal and exposure doses. The in vitro test-system such as
human cell culture and blood proteins allow for a short period to determine the level of
danger and identify potential risk from the receipt of metal citrates into the human organism.

Key words: microelements, nanoparticles, toxicity, cell culture, blood proteins.
Acknowledgments
This work was a fragment of research supported by the National Academy of Medical Sciences of
Ukraine.

4 International Scientific Conference Agrobiodiversity Nutrition, Health and Quality of Human and Bees Life |79
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September 11–13, 2019