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Toxicity of Copper Oxide (CuO) Nanoparticles on Human Blood Lymphocytes

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Abstract

CuO nanoparticles (CuO-NPs) serve several important functions in human life, particularly in the fields of medicine, engineering, and technology. These nanoparticles have been utilized as catalysts, semiconductors, sensors, gaseous and solid ceramic pigments, and magnet rotatable devices. Further use for CuO-NPs has been employed in the pharmaceutical industry especially in the production of anti-microbial fabric treatments or prevention of infections caused by Escherichia coli and methicillin-resistant Staphylococcus aureus. Two key potential routes of exposure to CuO-NPs exist through inhalation and skin exposure. Toxicity of these nanoparticles has been reported in various studies; however, no study as of yet has investigated the complete cellular mechanisms involved in CuO-NPs toxicity on human cells. The aim of this study was to determine the cytotoxicity of CuO-NPs on human blood lymphocytes. Blood lymphocytes were obtained from healthy male subjects through the use of Ficoll polysaccharide subsequently by gradient centrifugation. The following parameters were assayed in blood lymphocytes after a 6-h incubation with different concentrations of CuO-NPs: cell viability, reactive oxygen species (ROS) formation, lipid peroxidation, cellular glutathione levels, and mitochondrial and lysosomal damage. Our results demonstrate that CuO-NPs, in particular, decreased cell viability in a concentration-dependent manner and the IC50 determined was 382 μM. CuO-NP cytotoxicity was associated with significant increase at intracellular ROS level and loss of mitochondrial membrane potential and lysosomal membrane leakiness. Hence, CuO-NPs are shown to effectively induce oxidative stress in addition to inflict damage on mitochondria and lysosomes in human blood lymphocytes.

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References

  1. Ahamed M et al (2010) Genotoxic potential of copper oxide nanoparticles in human lung epithelial cells. Biochem Biophys Res Commun 396(2):578–583

    CAS  PubMed  Google Scholar 

  2. Akhtar MJ et al (2012) Protective effect of sulphoraphane against oxidative stress mediated toxicity induced by CuO nanoparticles in mouse embryonic fibroblasts BALB 3T3. J Toxicol Sci 37(1):139–148

    CAS  PubMed  Google Scholar 

  3. Akhtar MJ et al (2016) Dose-dependent genotoxicity of copper oxide nanoparticles stimulated by reactive oxygen species in human lung epithelial cells. Toxicol Ind Health 32(5):809–821

    CAS  PubMed  Google Scholar 

  4. Alarifi S et al (2013) Cytotoxicity and genotoxicity of copper oxide nanoparticles in human skin keratinocytes cells. Int J Toxicol 32(4):296–307

    PubMed  Google Scholar 

  5. Aruoja V et al (2009) Toxicity of nanoparticles of CuO, ZnO and TiO 2 to microalgae Pseudokirchneriella subcapitata. Sci Total Environ 407(4):1461–1468

    CAS  PubMed  Google Scholar 

  6. Baek Y-W, An Y-J (2011) Microbial toxicity of metal oxide nanoparticles (CuO, NiO, ZnO, and Sb 2 O 3) to Escherichia coli, Bacillus subtilis, and Streptococcus aureus. Sci Total Environ 409(8):1603–1608

    CAS  PubMed  Google Scholar 

  7. Bao S et al (2015) Assessment of the toxicity of CuO nanoparticles by using Saccharomyces cerevisiae mutants with multiple genes deleted. Appl Environ Microbiol 81(23):8098–8107

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Chen J et al (2008) Differential cytotoxicity of metal oxide nanoparticles. J Exp Nanosci 3(4):321–328

    CAS  Google Scholar 

  9. Cho W-S et al (2011) Progressive severe lung injury by zinc oxide nanoparticles; the role of Zn 2+ dissolution inside lysosomes. Particle and fibre toxicology 8(1):1

    CAS  Google Scholar 

  10. Dunphy Guzman KA et al (2006) Environmental risks of nanotechnology: national nanotechnology initiative funding, 2000-2004. Environmental Science & Technology 40(5):1401–1407

    CAS  Google Scholar 

  11. Dziembaj R et al (2011) Optimization of Cu doped ceria nanoparticles as catalysts for low-temperature methanol and ethylene total oxidation. Catal Today 169(1):112–117

    CAS  Google Scholar 

  12. Fahmy B, Cormier SA (2009) Copper oxide nanoparticles induce oxidative stress and cytotoxicity in airway epithelial cells. Toxicol in Vitro 23(7):1365–1371

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Faklaris O et al (2009) Photoluminescent diamond nanoparticles for cell labeling: study of the uptake mechanism in mammalian cells. ACS Nano 3(12):3955–3962

    CAS  PubMed  Google Scholar 

  14. Gaetke LM, Chow CK (2003) Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology 189(1):147–163

    CAS  PubMed  Google Scholar 

  15. Gilmour MI et al (2006) How exposure to environmental tobacco smoke, outdoor air pollutants, and increased pollen burdens influences the incidence of asthma. Environ Health Perspect 114:627–633

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Goya G et al (2008) Dendritic cell uptake of iron-based magnetic nanoparticles. Cell Biol Int 32(8):1001–1005

    CAS  PubMed  Google Scholar 

  17. Grassian VH et al (2007) Inflammatory response of mice to manufactured titanium dioxide nanoparticles: comparison of size effects through different exposure routes. Nanotoxicology 1(3):211–226

    CAS  Google Scholar 

  18. Heinlaan M et al (2008) Toxicity of nanosized and bulk ZnO, CuO and TiO 2 to bacteria Vibrio fischeri and crustaceans Daphnia magna and Thamnocephalus platyurus. Chemosphere 71(7):1308–1316

    CAS  PubMed  Google Scholar 

  19. Helland A et al (2008) Reviewing the environmental and human health knowledge base of carbon nanotubes. Ciência & Saúde Coletiva 13(2):441–452

    Google Scholar 

  20. Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74(1):214–226

    CAS  PubMed  Google Scholar 

  21. Holman MW, Lackner DI (2006) The nanotech report, 4th edn. Lux Research, Inc., New York

  22. Jin C-Y et al (2008) Cytotoxicity of titanium dioxide nanoparticles in mouse fibroblast cells. Chem Res Toxicol 21(9):1871–1877

    CAS  PubMed  Google Scholar 

  23. Karlsson HL et al (2008) Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 21(9):1726–1732

    CAS  PubMed  Google Scholar 

  24. Kawanishi S et al (1989) Hydroxyl radical and singlet oxygen production and DNA damage induced by carcinogenic metal compounds and hydrogen peroxide. Biol Trace Elem Res 21(1):367–372

    CAS  PubMed  Google Scholar 

  25. Kim JS et al (2011) Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model. Particle and fibre toxicology 8(1):1

    Google Scholar 

  26. Lei R et al (2015) Mitochondrial dysfunction and oxidative damage in the liver and kidney of rats following exposure to copper nanoparticles for five consecutive days. Toxicology Research 4(2):351–364

    CAS  Google Scholar 

  27. Li N et al (2003) Particulate air pollutants and asthma: a paradigm for the role of oxidative stress in PM-induced adverse health effects. Clin Immunol 109(3):250–265

    CAS  PubMed  Google Scholar 

  28. Martin CR (1994) Nanomaterials—a membrane-based synthetic approach, DTIC Document

    Google Scholar 

  29. Madhav MR et al (2017) Toxicity and accumulation of Copper oxide (CuO) nanoparticles in different life stages of Artemia salina. Environ Toxicol Pharmacol 52:227–238

    CAS  PubMed  Google Scholar 

  30. Midander K et al (2009) Surface characteristics, copper release, and toxicity of nano-and micrometer-sized copper and copper (II) oxide particles: a cross-disciplinary study. Small 5(3):389–399

    CAS  PubMed  Google Scholar 

  31. Nel AE et al (2009) Understanding biophysicochemical interactions at the nano–bio interface. Nat Mater 8(7):543–557

    CAS  PubMed  Google Scholar 

  32. Pettibone JM et al (2008) Inflammatory response of mice following inhalation exposure to iron and copper nanoparticles. Nanotoxicology 2(4):189–204

    Google Scholar 

  33. Piret J-P et al (2012) Copper (II) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response. Nano 4(22):7168–7184

    CAS  Google Scholar 

  34. Pourahmad J et al (2009) Biological reactive intermediates that mediate dacarbazine cytotoxicity. Cancer Chemother Pharmacol 65(1):89–96

    CAS  PubMed  Google Scholar 

  35. Pourahmad J et al (2011) Involvement of lysosomal labilisation and lysosomal/mitochondrial cross-talk in diclofenac induced hepatotoxicity. Iran J Pharm Res 10(4):877–887

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Pourahmad J et al (2010) Protective effects of fungal β-(1→ 3)-D-glucan against oxidative stress cytotoxicity induced by depleted uranium in isolated rat hepatocytes. Hum Exp Toxicol 30(3):173–181

    Google Scholar 

  37. Sarkar A et al (2011) Nano-copper induces oxidative stress and apoptosis in kidney via both extrinsic and intrinsic pathways. Toxicology 290(2):208–217

    PubMed  Google Scholar 

  38. Semisch A et al (2014) Cytotoxicity and genotoxicity of nano-and microparticulate copper oxide: role of solubility and intracellular bioavailability. Particle and fibre toxicology 11(1):1

    Google Scholar 

  39. Siddiqui MA et al (2013) Copper oxide nanoparticles induced mitochondria mediated apoptosis in human hepatocarcinoma cells. PLoS One 8(8):e69534

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Studer AM et al (2010) Nanoparticle cytotoxicity depends on intracellular solubility: comparison of stabilized copper metal and degradable copper oxide nanoparticles. Toxicol Lett 197(3):169–174

    CAS  PubMed  Google Scholar 

  41. Sun J et al (2011) Cytotoxicity, permeability, and inflammation of metal oxide nanoparticles in human cardiac microvascular endothelial cells. Cell Biol Toxicol 27(5):333–342

    PubMed  Google Scholar 

  42. Wang H et al (2004) Fabrication and characterization of copper nanoparticle thin-films and the electrocatalytic behavior. Anal Chim Acta 526(1):13–17

    CAS  Google Scholar 

  43. Wang Z et al (2012) CuO nanoparticle interaction with human epithelial cells: cellular uptake, location, export, and genotoxicity. Chem Res Toxicol 25(7):1512–1521

    CAS  PubMed  Google Scholar 

  44. Wasowicz W et al (1993) Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin Chem 39(12):2522–2526

    CAS  PubMed  Google Scholar 

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Author notes

  1. Evelyn Assadian and Mohammad Hadi Zarei contributed equally to this study.

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Guilan University, Guilan, P. O. Box: 41335-1914, Rasht, Iran

    Evelyn Assadian, Ali Ghanadzadeh Gilani & Hamid Degampanah

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, P.O. Box 14155-6153, Tehran, Iran

    Evelyn Assadian, Mohammad Hadi Zarei, Mehrzad Farshin & Jalal Pourahmad

Authors
  1. Evelyn Assadian
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  2. Mohammad Hadi Zarei
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  3. Ali Ghanadzadeh Gilani
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  4. Mehrzad Farshin
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  5. Hamid Degampanah
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  6. Jalal Pourahmad
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Correspondence to Hamid Degampanah or Jalal Pourahmad.

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Assadian, E., Zarei, M.H., Gilani, A.G. et al. Toxicity of Copper Oxide (CuO) Nanoparticles on Human Blood Lymphocytes. Biol Trace Elem Res 184, 350–357 (2018). https://doi.org/10.1007/s12011-017-1170-4

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  • DOI: https://doi.org/10.1007/s12011-017-1170-4

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