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Pharmaceutical Nanotechnology

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ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

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Research Article

Features of Bioaccumulation and Toxic Effects of Copper (II) Oxide Nanoparticles Under Repeated Oral Exposure in Rats

Author(s): Mark Sergeevich Stepankov, Marina Aleksandrovna Zemlyanova*, Nina Vladimirovna Zaitseva, Anna Mikhailovna Ignatova and Alena Evgenievna Nikolaeva

Volume 9, Issue 4, 2021

Published on: 28 July, 2021

Page: [288 - 297] Pages: 10

DOI: 10.2174/2211738509666210728163901

Price: $65

Abstract

Background: Currently, the range of copper (II) oxide nanoparticles’ (CuO NPs) applications is expanding and the global production of CuO NPs is increasing. In this regard, the risk of exposure of the population to this nanomaterial is increasing.

Objective: The aim of the study is to investigate the patterns of bioaccumulation and toxic effects of CuO NPs after multiple oral exposures.

Methods: The particle size was determined by scanning electron microscopy and dynamic laser light scattering. The specific surface area was measured by the method of Brunauer, Emmett, Teller. Total pore volume - by the method of Barrett, Joyner, Khalenda. Twenty-four hours after the final exposure, blood samples were taken for biochemical and hematological analysis, and internal organs were taken to determine their mass, copper concentration and histological analysis. The study was carried out in comparison with copper (II) oxide microparticles (CuO MPs).

Results: In terms of size, surface area, and pore volume, the studied copper (II) oxide sample is a nanomaterial. The median lethal dose of CuO NPs was 13187.5 mg/kg of body weight. Bioaccumulation occurs in the stomach, blood, intestines, liver, lungs, kidneys and brain. Pathomorphological changes in the liver are manifested in the form of necrosis, degeneration, hepatitis; kidney - proliferation of mesangial cells, dystrophy; stomach - gastritis; small intestine - hyperplasia, enteritis; large intestine - colitis; lungs - hyperplasia, abscess, pneumonia, bronchitis, vasculitis. Clumps of brown pigment were detected in the kidneys, stomach and lungs. The mass of the stomach and intestines increased, the mass of the liver, kidneys and lungs decreased. Pathomorphological changes in organs are likely to cause an increase in the levels of activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, amylase, malondialdehyde concentration and a decrease in plasma antioxidant activity. The proportion of segmented neutrophils and the number of leukocytes are raised, the proportion of lymphocytes is reduced.

Conclusion: The degree of bioaccumulation and toxicity of CuO NPs are more expressed in relation to CuO MPs.

Keywords: Copper (II) oxide, nanoparticles, microparticles, oral exposure, toxicity, rats.

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[1]
Benefits and applications. National Nanotechnology Initiative. Available from: https://www.nano.gov/you/nanotechnology-benefits [Cited 13.07.2020]
[2]
Sukhanova A, Bozrova S, Sokolov P, Berestovoy M, Karaulov A, Nabiev I. Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale Res Lett 2018; 13(1): 44.
[http://dx.doi.org/10.1186/s11671-018-2457-x] [PMID: 29417375]
[3]
Grigore ME, Biscu ER, Holban AM, Gestal MC, Grumezescu AM. Methods of synthesis, properties and biomedical applications of cuo nanoparticles. Pharmaceuticals (Basel) 2016; 9(4): 1-14.
[http://dx.doi.org/10.3390/ph9040075] [PMID: 27916867]
[4]
Cohen D, Soroka Y, Ma’or Z, et al. Evaluation of topically applied copper(II) oxide nanoparticle cytotoxicity in human skin organ culture. Toxicol. In Vitro 2013; 27(1): 292-8.
[http://dx.doi.org/10.1016/j.tiv.2012.08.026] [PMID: 22954531]
[5]
Copper oxide (cuo) nanoparticles - properties, applications Azonano. Available from: https://www.azonano.com/article.aspx?ArticleID=3395 [Cited 03.09.2020]
[6]
Ameh T, Sayes CM. The potential exposure and hazards of copper nanoparticles: a review. Environ Toxicol Pharmacol 2019; 71: 103220.
[http://dx.doi.org/10.1016/j.etap.2019.103220] [PMID: 31306862]
[7]
Luis de la Fuente J. Mesoporous copper oxide as a new combustion catalyst for composite propellants. J Propuls Power 2013; 29(2): 293-8.
[http://dx.doi.org/10.2514/1.B34491]
[8]
Hou J, Wang X, Hayat T, Wang X. Ecotoxicological effects and mechanism of CuO nanoparticles to individual organisms. Environ Pollut 2017; 221: 209-17.
[http://dx.doi.org/10.1016/j.envpol.2016.11.066] [PMID: 27939631]
[9]
De Jong WH, De Rijk E, Bonetto A, et al. Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats. Nanotoxicology 2019; 13(1): 50-72.
[http://dx.doi.org/10.1080/17435390.2018.1530390] [PMID: 30451559]
[10]
Privalova LI, Katsnelson BA, Loginova NV, 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.
[http://dx.doi.org/10.3390/ijms150712379] [PMID: 25026171]
[11]
Sarkar A, Das J, Manna P, Sil PC. Nano-copper induces oxidative stress and apoptosis in kidney via both extrinsic and intrinsic pathways. Toxicology 2011; 290(2-3): 208-17.
[http://dx.doi.org/10.1016/j.tox.2011.09.086] [PMID: 22000994]
[12]
Karlsson HL, Cronholm P, Gustafsson J, Möller L. Copper oxide nanoparticles are highly toxic: A comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 2008; 21(9): 1726-32.
[http://dx.doi.org/10.1021/tx800064j] [PMID: 18710264]
[13]
Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 2016; 1863(12): 2977-92.
[http://dx.doi.org/10.1016/j.bbamcr.2016.09.012] [PMID: 27646922]
[14]
Strauch BM, Hubele W, Hartwig A. Impact of endocytosis and lysosomal acidification on the toxicity of copper oxide nano- and microsized particles: uptake and gene expression related to oxidative stress and the dna damage response. Nanomaterials (Basel) 2020; 10(4): 1-15.
[http://dx.doi.org/10.3390/nano10040679] [PMID: 32260290]
[15]
Zhang J, Zou Z, Wang B, et al. Lysosomal deposition of copper oxide nanoparticles triggers HUVEC cells death. Biomaterials 2018; 161: 228-39.
[http://dx.doi.org/10.1016/j.biomaterials.2018.01.048] [PMID: 29421558]
[16]
Maciel-Magalhães M, Medeiros RJ, Bravin JS, et al. Evaluation of acute toxicity and copper accumulation in organs of Wistar rats, 14 days after oral exposure to copper oxide (II) nano- and microparticles. J Nanopart Res 2020; 22(2): 1-11.
[http://dx.doi.org/10.1007/s11051-019-4721-0]
[17]
Perreault F, Pedroso Melegari S, Henning da Costa C, de Oliveira Franco Rossetto AL, Popovic R, Gerson Matias W. Genotoxic effects of copper oxide nanoparticles in Neuro 2A cell cultures. Sci Total Environ 2012; 441: 117-24.
[http://dx.doi.org/10.1016/j.scitotenv.2012.09.065] [PMID: 23137976]
[18]
Naz S, Gul A, Zia M. Toxicity of copper oxide nanoparticles: a review study. IET Nanobiotechnol 2020; 14(1): 1-13.
[http://dx.doi.org/10.1049/iet-nbt.2019.0176] [PMID: 31935671]
[19]
Greg S, Sing K. Adsorption, specific surface area, porosity. Academic Press: London 1984; p. 306.
[20]
Barrett EP, Joyner LG, Halenda PP. The determination of pore volume and area distributions in porous substances. I. Computations from nitrogen isotherms. J Am Chem Soc 1951; 73: 373-80.
[http://dx.doi.org/10.1021/ja01145a126]
[21]
Lim RK, Rink KG, Glass HG, Soaje-Echague E. A method for the evaluation of cumulation and tolerance by the determination of acute and subchronic median effective doses. Arch Int Pharmacodyn Ther 1961; 130: 336-53.
[PMID: 13762162]
[22]
Copper (II) oxide nanopowder material safety data sheet (MSDS). Sigma-Aldrich 2019; Available at: https://www.sigmaaldrich.com/PK/en/substance/copperiioxide79551317380.
[23]
Copper (II) oxide powder material safety data sheet (MSDS). Sigma-Aldrich 2019; Available at https://www.sigmaaldrich.com/PK/en/substance/copperiioxide79551317380.
[24]
Peng C, Shen C, Zheng S, et al. Transformation of CuO nanoparticles in the aquatic environment: influence of pH, electrolytes and natural organic matter. Nanomaterials (Basel) 2017; 7(10): 1-16.
[http://dx.doi.org/10.3390/nano7100326] [PMID: 29036921]
[25]
Lee I-C, Ko J-W, Park S-H, et al. Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles. Part Fibre Toxicol 2016; 13(1): 56.
[http://dx.doi.org/10.1186/s12989-016-0169-x] [PMID: 27788687]
[26]
Yahya RAM, Attia AM, El-Banna SG, et al. Hematotoxicity induced by copper oxide and/or zinc oxide nanoparticles in male albino rats. J Biotechnol 2019; 3(4): 1-7.
[27]
El Bialy BE, Hamouda RA, Abd Eldaim MA, et al. Comparative toxicological effects of biologically and chemically synthesized copper oxide nanoparticles on mice. Int J Nanomedicine 2020; 15: 3827-42.
[http://dx.doi.org/10.2147/IJN.S241922] [PMID: 32581533]
[28]
Khatami M. Developmental phases of inflammation-induced massive lymphoid hyperplasia and extensive changes in epithelium in an experimental model of allergy: Implications for a direct link between inflammation and carcinogenesis. Am J Ther 2005; 12(2): 117-26.
[http://dx.doi.org/10.1097/01.mjt.0000143699.91156.21] [PMID: 15767829]
[29]
Strukov AI, Serov VV. Pathological anatomy a textbook. 5th ed. Moscow: Litterra 2010; pp. 54-63.
[30]
Nazarenko GI, Kishkun AA. Clinical evaluation of laboratory results.Meditsina: Moscow 2006; pp. 162-6.
[31]
Abboud HE. Mesangial cell biology. Exp Cell Res 2012; 318(9): 979-85.
[http://dx.doi.org/10.1016/j.yexcr.2012.02.025] [PMID: 22414873]
[32]
Cove-Smith A, Hendry BM. The regulation of mesangial cell proliferation. Nephron, Exp Nephrol 2008; 108(4): e74-9.
[http://dx.doi.org/10.1159/000127359] [PMID: 18431073]
[33]
Brzóska MM, Moniuszko-Jakoniuk J, Piłat-Marcinkiewicz B, Sawicki B. Liver and kidney function and histology in rats exposed to cadmium and ethanol. Alcohol Alcohol 2003; 38(1): 2-10.
[http://dx.doi.org/10.1093/alcalc/agg006] [PMID: 12554600]
[34]
Fahmy B, Cormier SA. Copper oxide nanoparticles induce oxidative stress and cytotoxicity in airway epithelial cells. Toxicol. In Vitro 2009; 23(7): 1365-71.
[http://dx.doi.org/10.1016/j.tiv.2009.08.005] [PMID: 19699289]
[35]
Wang Z, Li N, Zhao J, White JC, Qu P, Xing B. CuO nanoparticle interaction with human epithelial cells: Cellular uptake, location, export, and genotoxicity. Chem Res Toxicol 2012; 25(7): 1512-21.
[http://dx.doi.org/10.1021/tx3002093] [PMID: 22686560]
[36]
Thit A, Selck H, Bjerregaard HF. Toxic mechanisms of copper oxide nanoparticles in epithelial kidney cells. Toxicol in vitro 2015; 29(5): 1053-9.
[http://dx.doi.org/10.1016/j.tiv.2015.03.020] [PMID: 25862124]
[37]
Alarifi S, Ali D, Verma A, Alakhtani S, Ali BA. Cytotoxicity and genotoxicity of copper oxide nanoparticles in human skin keratinocytes cells. Int J Toxicol 2013; 32(4): 296-307.
[http://dx.doi.org/10.1177/1091581813487563] [PMID: 23667135]
[38]
Keshavarzi M, Khodaei F, Siavashpour A, Saeedi A, Mohammadi-Bardbori A. Hormesis effects of nano- and micro-sized copper oxide. Iran J Pharm Res 2019; 18(4): 2042-54.
[http://dx.doi.org/10.22037/ijpr.2019.13971.12030] [PMID: 32184868]
[39]
Anreddy RNR. Copper oxide nanoparticles induces oxidative stress and liver toxicity in rats following oral exposure. Toxicol Rep 2018; 5: 903-4.
[http://dx.doi.org/10.1016/j.toxrep.2018.08.022] [PMID: 30191135]

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