You are using an outdated browser. For a faster, safer browsing experience, upgrade for free today.

Investigation of the safety of iron and copper nanopreparations on human blood plasma proteins in vitro

ISSN 2223-6775 Ukrainian journal of occupational health Vol.17, No 3, 2021


https://doi.org/10.33573/ujoh2021.03.139

Investigation of the safety of iron and copper nanopreparations on human blood plasma proteins in vitro

N.M. Dmytrukha1, O.S. Lahutina1, T.Yu. Gromovoy2, E.V. Pylypchuk3
1State Institution ”Kundiev Institute of Occupational Health of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
2Chuiko Institute of Surfase Chemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
3Stockholm University, Departament of Materials and Environmental Chemistry, Stockholm, Sweden


Full article (PDF)

Introduction. Today nanotechnological preparations of micronutrients in the form of nanoparticles (NP) and nanoaquachelativ (NAСH) are used in medicine, veterinary medicine, agriculture, perfumes and food products. Nanoscale causes increased bioavailability and biological activity of trace elements, which can have both positive and negative effects on human health. Thith is due to the special physicochemical properties of the NPs, their large surface area and adsorption capacity. It is established that at interaction of nanoparticles with proteins there are disturbances of their structural organization (denaturation). To prevent adverse effects from the use of such nanopreparations, it is necessary to perform toxicological studies of their safety.

The aim of the study was to evaluate the safety of iron and copper nanopreparations (metal nanoparticles and their nanoaquachelates) on the structure of human blood plasma proteins in experiment in vitro.

Materials and methods. The object of the study were aqueous dispersions of nanoparticles of iron and copper (NP Fe 40 nm and NP Cu 20 nm), chemically synthesized and nanoaquachelates (NACH Fe and NACH Cu particle size 200 nm), obtained by erosion-explosive nanotechnology. The study was performed on human plasma proteins (albumin, IgG) under conditions of their in vitro exposure to these nanopreparations. Changes in the structure of proteins were evaluated by the optical density of solutions on Mephane spectrophotometer at 405 nm and the mass spectrs of proteins by MALDI-ToF mass-spectrometry on an Autoflex II - (Bruker).

Results. It has been shown that the interaction of NP and NACН of metals leads to changes in the structure and mass of proteins. It was found that the optical density indices of protein solutions changed depending on the concentration of metal NP, their size, and the activity of the base metal.Thus, NP Cu and HACH Cu interacted more actively with albumin, while NP Fe and HACH Fe - with immunoglobulin G. It was shown that metals in the form of nanoparticels size <100 nm caused more intensive structural changes in proteins than their HACH with particles size of 200 nm. Based on the obtained results, safe concentrations of metals NPs were calculated: NP Fe -0.06 mg / ml, NP Cu - 0.03 mg / ml, HACH Fe and HACH Cu - 0.1 mg / ml.

Conclusions. The NP and HACH of iron and copper incubated with albumin and human IgG in vitro caused structural changes in both proteins and NPs. Proteins increased the solubility of NPs, which caused the release of metal ions, their attachment to the active groups of proteins, as evidenced by changes in the optical density of solutions and an increase in the mass of proteins. Due to the large surface area, metal NPs adsorbed proteins on themselves, causing their aggregation and precipitation. The results obtained make it possible to recommend blood plasma proteins as an in vitro model for the express assessment of the safety and biocompatibility of microelement nanopreparations for human and animal health, as well as during their hygienic regulation.

Key words: iron, copper, nanoparticles, nanoaquachelates, albumin, immunoglobulin G, toxicity, biocompatibility.

References

  1. Skal'nyj A.V., Rudakov I.A. (2004). Bioelementy v medicine M. : Izdatel'skij dom «Oniks 21 vek»: Mir. 272 s.
  2. Bondarev L.G. (1984). . Mikroelementy - blago i zlo Znanie. , 142 s.
  3. Avcin A.P., Zhavoronkov A.A., Rish M.A., Strochkova L.S. (1996). Mikroelementozy cheloveka: etiologiya, klassifikaciya, organopatologiya. Moskva: Medicina. 192 s.
  4. Chekman I.S. Nanochastynky: vlastyvosti ta perspektyvy zastosuvannia (2009). biokhimichnyi zhurnal. T. 81, No 1, S. 122-129.
  5. Borisevich V.B., Kaplunenko V.G., Kosinov N.V. [i dr.]: pod redakciej V.B. Borisevicha, V.G. Kaplunenko (2012). Nanomaterialy i nanotekhnologii v veterinarnoj praktike. K.: VD «Avycena». 512 s. ISBN978-966-2144-40-6
  6. Hulich M.P., Yemchenko N.L., Kaplunenko V.H., Kosinov M.V., Kharchenko O.O. (2011) Perspektyvy zastosuvannia tsytrativ biometaliv, otrymanykh za akvananotekhnolohiieiu yak sposib podolannia defitsytu makro - i mikroelementiv Tezy dopovidei mizhnarodnoho seminaru «Etyka nanotekhnolohii ta nanobezpeka» 13 zhovtnia 2011, Kyiv, Ukraina. 46.
  7. Kolesnichenko A.V., Timofeev M.V., Protopopova M.V. (2008). Toksichnost' nanomaterialov - 15 let issledovanij. Rossijskie nanotekhnologii. Tom 3, 3-4.
  8. Trakhtenberh I.M., Dmytrukha N.M., Korolenko T.K., Lahutina O.S., Lehkostup L.A. (2017). Mikroelementy u nanorozmirnomu stani, osoblyvosti biolohichnoi dii, otsinka bezpechnosti. Biulleten XVI chtenyi i V.V. Podvysotskoho 18-19 maia 2017, Odessa, 2017, Tom 1, 348-350.
  9. Trakhtenberg I.M., Dmytrukha N.M. (2013), Nanoparticles of metals, methods of definition, spheres of use, physico-chemical and toxic properties. Ukrainian Journal of Occupational Health, 37 (4), 62-74. https://doi.org/10.33573/ujoh2013.04.062
  10. Chekman I.S., Serdiuk A.M., Kundiiev Yu.I., [ta in.] (2009). Nanotoksykolohiia: napriamky doslidzhen (ohliad). Dovkillia ta zdorovia.1(48), 2009, 3-7.
  11. Prodanchuk N.G., Balan M. (2009), "Nanotoxicology: State and perspectives of investigations",Modern problems of toxicology,3-4, 4-18.
  12. Kartel M.T., Tereshchenko P. (2008), "The concept of methodology for identification and toxicological studies of nanomaterials and risk assessment for the human body and the environment in their production and use", Collection of scientific works, Khimiia, fizika i tekhnologhia hjverkhnosti, Naukova dumka, Kyiv, 14, 565-583.
  13. Dmytrukha N. M., Lahutyna O. S., Korolenko T.K., Dybkova S.M., Hromovyi T.Iu.(2019). Zastosuvannia alternatyvvnykh modelei ta metodiv in vitro dlia otsinky bezpeky nanochastynok metaliv. Biuleten XVIII chytan im. V.V.Pidvysotskoho 21-22 travnia 2019 r., Odesa, 2019, S.65-67.
  14. Lukyanov A.S., Semina T.K., Korolev A.M. (2006). Prediction of parameters of acute toxicity of chemical compounds by conformation changes in proteins in vitro. Meditsina truda i promyshlennaya ekologiya, 5, 33-40.
  15. Prokopenko V.V., Naboka Yu.N., Metelica L.A. [i dr.] (1999). Chuvstvitel'nost' molekulyarnyh, nadmolekulyarnyh i kletochnyh bioob"ektov k kationam tyazhelyh metallov. Sovremennye problemy toksikologii, T.3,18-21.
  16. Chekunova M.P., Frolova A.D. (1986), "Modern concepts on the biological action of metals",Gigiyenai sanitaria,12, 18-21.
  17. Trachtenberg I. M., Pokrovsky V.O., Dmytrukha N.M., GromovyiYu., Shevchenko G.V. (2009), "Investigations on the effect of heavy metal compounds on human serum immunoglobulin by MALDI-TOF mass spectrometry", Modern problems of toxicology,1, 37-41.
  18. Dmytrukha N.M., Lahutina O.S., Gromovoy T.Yu. (2020), Investigation of the influence of lead compounds with particles of different dispersity on human blood plasma proteins as an express method for evaluation of their safety. Ukrainian Journal of Occupational Health, 16(3), 202-209. https://doi.org/10.33573/ujoh2020.03.202
  19. Hardman R. (2006). A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental Environ. Health Perspect., 114(2), 165-172. https://doi.org/10.1289/ehp.8284
  20. Zhang, J., Ma, X., Guo, Y., Yang, L., Shen, Q., Wang, H., & Ma, Z. (2010). Size-controllable preparation of bovine serum albumin-conjugated PbS nanoparticles. Materials Chemistry andPhysics, 119(1), 112-117. https://doi.org/10.1016/j.matchemphys.2009.08.027
  21. Kolloidno-himicheskie osnovy nanonauki (2005).: pod red. A.P. SHpaka, Z.R. Ul'berg. - K.: Akademperiodika. 466 s.
  22. Patent Ukrainy na korysnu model No 38391. Sposib otrymannia karboksylativ metaliv «Nanotekhnolohiia otrymannia karboksylativ metaliv» // Kosinov M.V., Kaplunenko V.H. / MPK (2006): C07C 51/41, C07F 5/00, C07F 15/00, C07C 53/126 (2008.01), C07C 53/10 (2008.01), A23L 1/00, B82B 3/00. 12.01.2009, biul. No 1/2009.
  23. Glen L. Hortin (2006). The MALDI TOF Mass Spectrometric View of the Plasma Proteome and Peptidome. Clinical Chemistry. 57(22), 1-11. https://doi.org/10.1373/clinchem.2006.069252
  24. Porublyova L.V., Rebriev A.V., Gromoviy T.Yu., Minya I.Y., Obolenska M.Yu. (2009). "MALDI - TOF mass spectrometry in the study of macromolecular biological compounds", Ukrainian Biochemical Journal, 81(3), 46-57.
  25. High Mass Linear Analasis of Intact Proteins on the 4800 MALDI TOF/TOF Ayalyzer. TechnicalNote appliedbiosystems.com].
  26. Lujk A.M., Luk'yanchuk V.D. (1984). Syvorotochnyj al'bumin i biotranspor yadov. M.: Medicina, 224 s.
  27. Kharazian B., Hadipour N.L., Ejtehadi M.R. (2016), Understanding the nanoparticle-protein corona complexes using computational and experimental methods. Biochem Cell Biol., 75, 162- 174. https://doi.org/10.1016/j.biocel.2016.02.008
  28. Lundqvist M, Augustsson C, Lilja M, Lundkvist K, Dahlbäck B, Linse S, et al. (2017) The nanoparticle protein corona formed in human blood or human blood fractions. PLoS ONE12(4): e0175871. https://doi.org/10.1371/journal.pone.0175871