Features of bioaccumulation and toxic effects of copper (II) oxide nanoparticles under repeated inhalation exposure in rats

Introduction. Active use in various spheres of economic activity, large-scale production and the availability of data on toxicity determine the relevance of studying the effects of copper (II) oxide nanoparticles (CuO NPs) on the body during inhalation exposure.

Material and Methods. The size, surface area, and pore volume of CuO NPs were determined. The study and assessment of biochemical and hematological parameters of blood, the degree of bioaccumulation of nanomaterial, pathomorphological changes in organs of rats exposed to CuO NPs were carried out. The studies were carried out in comparison with a microsized analogue (CuO MPs).

Results. The size of CuO NPs in the composition of the native powder is 305.00 times less than that of CuO MPs. The surface area and pore volume are 9.61 and 9.33 times larger, respectively. After exposure to CuO NPs in the blood of rats relative to the control, the levels of activity of ALT, AST, ALP, GGT, LDH, amylase, AOA, MDA and the concentration of CRP increased by 1.49-2.23 times, the content of urea decreased by 1.41 times; relative number of eosinophils, leukocyte count, RDW by 1.31-5.39 times increased, relative number of segmented neutrophils decreased by 1.37 and monocytes by 1.42 times. The effect of NPs, in comparison with MPs, is more pronounced in increasing the activity of ALT, AST, LDH, MDA and the concentration of CRP by 1.25-1.68 times and in reducing the concentration of urea by 1.21 times; in increase the relative number of eosinophils by 2.37 and the count of leukocytes by 1.61 times. The concentration of copper under the action of NPs increases relative to the control in the lungs, liver, stomach, intestines and kidneys by 1.59-6.99 times. The degree of bioaccumulation of nanoparticles is 1.20-2.12 times higher than that of microparticles in the lungs, liver, stomach, and kidneys.

Conclusion. Functional and pathomorphological changes caused by CuO NPs are more pronounced in the lungs, stomach, and small intestine in comparison with microparticles. It was confirmed that the studied CuO particles are nanomaterials. They have a more pronounced bioaccumulation and toxic effect relative to the microdispersed analogue.

Contribution:

Zaitseva N.V. — the concept and design of the study, statistical processing of the material, editing;

Zemlyanova M.A. — the concept and design of the study, processing of the material, writing the text;

Stepankov M.S. — collection of material, writing the text;

Ignatova A.M., Nikolaeva A.E. — processing of the material.

All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The study had no sponsorship.

Received: July 7, 2021 / Accepted: September 28, 2021 / Published: October 31, 2021

1. Ishakova E., Ishakov O. World market for n nanomaterials: structure and trends. MATEC Web Conf. 2017; 129: 1-5. https://doi.org/10.1051/matecconf/201712902013

2. Allied Market Research. Europe nanomaterials market by type of material, by end user - opportunity analysis and industry forecast, 2014-2022. Available at: https://www.alliedmarketresearch.com/europe-nanomaterials-market

3. Sukhanova A., Bozrova S., Sokolov P., Beresovoy M., Karaulov A., Nabiev I. Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale Res. Lett. 2018; 13(1): 44. https://doi.org/10.1186/s11671-018-2457-x

4. Ameh T., Sayes C.M. The potential exposure and hazards of copper nanoparticles: A review. Environ. Toxicol. Pharmacol. 2019; 71: 103220. https://doi.org/10.1016/j.etap.2019.103220

5. Azonano. Copper Oxide (CuO) nanoparticles - Properties, Applications. Available at: https://www.azonano.com/article.aspx?ArticleID=3395

6. Hou J., Wang X., Hayat T., Wang X. Ecotoxicological effects and mechanism of CuO nanoparticles to individual organisms. Environ. Pollut. 2017; 221: 209-17. https://doi.org/10.1016/j.envpol.2016.11.066

7. Sarkar A., Das J., Manna P., Sil P.S. Nano-copper induces oxidative stress and apoptosis in kidney via both extrinsic and intrinsic pathways. Toxicology. 2011; 290(2-3): 208-17. https://doi.org/10.1016/j.tox.2011.09.086

8. Zhang J., Zou Z., Wang B., Xu G., Wu Q., Zhang Y., et al. Lysosomal deposition of copper oxide nanoparticles triggers HUVEC cells death. Biomaterials. 2018; 161: 228-39. https://doi.org/10.1016/j.biomaterials.2018.01.048

9. Privalova L.I., Katsnelson B.A., Loginova N.V., Gurvich V.B., Shur V.Y., Valamina I.E., et al. Subchronic toxicity of copper oxide nanoparticles and its attenuation with the help of a combination of bioprotectors. Int. J. Mol. Sci. 2014; 15(7): 12379-406. https://doi.org/10.3390/ijms150712379

10. Perreault F., Pedroso Melegari S., Henning da Costa C., de Oliveira Franco Rossetto A.L., Popovic R., Gerson Matias W. Genotoxic effects of copper oxide nanoparticles in Neuro 2A cell cultures. Sci. Total Environ. 2012; 441: 117-24. https://doi.org/10.1016/j.scitotenv.2012.09.065

11. Naz S., Gul A., Zia M. Toxicity of copper oxide nanoparticles: a review study. IET Nanobiotechnol. 2020; 14(1): 1-13. https://doi.org/10.1049/iet-nbt.2019.0176

12. Gregg S.J., Sing K.S.W. Adsorption, Surface Area and Porosity. London: Academic Press; 1982.

13. Barrett E.P., Joyner L.G., Halenda P.P. The determination of pore volume and area distributions in porous substances. I. Computations from nitrogen isotherms. J. Am. Chem. Soc. 1951; 73: 373-80.

14. Gosens I., Cassee F.R., Zanella M., Manodori L., Brunelli A., Costa A.L. et al. Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure. Nanotoxicology. 2016; 10(8): 1084-95. https://doi.org/10.3109/17435390.2016.1172678

15. Yahya R.A.M., Attia A.M., El-Banna S.G., El-Trass E.E., Azab A.E., Jbireal J.M., et al. Hematotoxicity induced by copper oxide and/or zinc oxide nanoparticles in male albino rats. J. Biotechnol. 2019; 3(4): 1-7.

16. El Bialy B.E., Hamouda R.A., Abd Eldaim M.A., El Ballal S.S., Heikal H.S., Khalifa H.K., et al. Comparative toxicological effects of biologically and chemically synthesized copper oxide nanoparticles on mice. Int. J. Nanomedicine. 2020; 15: 3827-42. https://doi.org/10.2147/IJN.S241922

17. Khatami M. Developmental phases of inflammation-induced massive lymphoid hyperplasia and extensive changes in epithelium is an experimental model of allergy: implications for a direct link between inflammation and carcinogenesis. Am. J. Ther. 2005; 12(2): 117-26. https://doi.org/10.1097/01.mjt.0000143699.91156.21

18. Abboud H.E. Mesangial cell biology. Exp. Cell Res. 2012; 318(9): 979-58. https://doi.org/10.1016/j.yexcr.2012.02.025

19. Nazarenko G.I., Kishkun A.A. Clinical Evaluation of Laboratory Research Results [Klinicheskaya otsenka rezul’tatov laboratornykh issledovaniy.]. Moscow: Meditsina; 2006

20. Goldklang M., Stockley R. Pathophysiology of Emphysema and Implications. Chronic. Obstr. Pulm. Dis. 2016; 3(1): 454-8. https://doi.org/10.15326/jcopdf.3.1.2015.0175

21. Anreddy R.N.R. Copper oxide nanoparticles induces oxidative stress and liver toxicity in rats following oral exposure. Toxicol. Rep. 2018; 5: 903-4. https://doi.org/10.1016/j.toxrep.2018.08.022