Skip to main content
Log in

Cytotoxicity and Genotoxicity of Copper oxide Nanoparticles in chickens

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Copper oxide nanoparticles (CuO-NPs) are consciously used to control the growth of bacteria, fungi, and algae. Several studies documented the beneficial and hazardous effects of CuO-NPs on human cells and different experimental animals but there are not many studies that report the effect of CuO-NPs in poultry. Therefore, the present study was performed to investigate the dose-dependent effects of copper oxide nanoparticles on the growth performance, immune status, oxidant/antioxidant capacity, DNA status, and histological structures of most edible parts of broiler chickens (muscle, heart, liver, spleen, and kidneys). The experiment was carried out on 90 1-day-old broiler chicks (Cobb 500) which were divided into three experimental groups (n = 30) in three replicates (n = 10). Group 1 was kept as a control group and did not receive copper oxide nanoparticles. Groups 2 and 3 received CuO-NPs by oral gavage at dose 5 mg/kg and 15 mg/kg bwt respectively at 1, 7, 14, 21, 28, and 35 days of the life of the chickens. An increase in the amount of feed intake and weight was recorded every week, and finally, the food conversion ratio (FCR) was calculated. Our results showed dose-dependent increases in malondialdehyde levels, copper contents, DNA fragmentation percent, and microscopic scoring in different examined organs of CuO-NPs-receiving groups associated with a remarkable reduction in weight gain, food conversion ratio, catalase activity, and antibody titer of both New Castle and Avian Influenza viruses. Histopathological alterations were observed in both groups receiving CuO-NPs with some variations in its severity. Our study concluded that CuO-NPs are considered cytotoxic and we recommend not adding them to poultry feed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

All data are available on request.

References

  1. Nriagu J, Boughanen M, Linder A, Howe A, Grant CH, Rattray R, Vutchov M, Lalor G (2009) Levels of As, Cd, Pb, Cu, Se and Zn in bovine kidneys and livers in Jamaica. Ecotoxicol Environ Saf 72(2):564–571

    Article  CAS  PubMed  Google Scholar 

  2. Pesti GM, Bakalli RI (1996) Studies on the feeding of cupric sulfate pentahydrate and cupric citrate to broiler chickens. Poult Sci 75:1086–1091

    Article  CAS  PubMed  Google Scholar 

  3. Kim B-E, Nevitt T, Thiele DJ (2008) Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol 4(3):176–185. https://doi.org/10.1038/nchembio.72

    Article  CAS  PubMed  Google Scholar 

  4. Bendeddouche B, Zellagui R, Bendeddouche E (2014) Levels of Selected Heavy Metals in Fresh Meat from Cattle, Sheep, Chicken and Camel Produced in Algeria. Annual Res Rev Biol 4(8):1260–1267

    Article  Google Scholar 

  5. Liu Z, Robinson JT, Sun X, Dai H (2008) PEGylated aanographene oxide for delivery of water-insoluble cancer drugs. J Am Chem Soc 2008(130):10876–10877

    Article  CAS  Google Scholar 

  6. Sun X, Liu Z, Welsher K, Robinson J, Goodwin A, Zaric S, Dai H (2008) Nano-graphene oxide for cellular imaging and drug delivery. Nano Res 1:203–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yang K, Zhang S, Zhang G, Sun X, Lee S-T, Liu Z (2010) Graphene in mice: Ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett 10:3318–3323

    Article  CAS  PubMed  Google Scholar 

  8. Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen X, Dai H (2008) Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res 68:6652–6660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Harhaji L, Isakovic A, Raicevic N, Markovic Z, Todorovic-Markovic B, Nikolic N, Vranjes-Djuric S, Markovic I, Trajkovic V (2007) Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene. Eur J Pharmacol 568:89–98

    Article  CAS  PubMed  Google Scholar 

  10. Khalaf AA, Hassanen EI, Azouz RA et al (2019) Ameliorative effect of zinc oxide nanoparticles against dermal toxicity induced by lead oxide in rats. Int J Nanomedicine 14:7729–7741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Keller AA, Adeleye AS, Conway JR, Garner KL, Zhao L, Cherr GN, Hong J, Gardea-Torresdey JL, Godwin HA, Hanna S (2017) Comparative environmental fate and toxicity of copper nanomaterials. NanoImpact 7:28–40

    Article  Google Scholar 

  12. Garner KL, Suh S, Lenihan HS, Keller AA (2015) Species sensitivity distributions for engineered nanomaterials. Environ Sci Technol 49:5753–5759

    Article  CAS  PubMed  Google Scholar 

  13. Wu F, Harper BJ, Crandon LE, Harper SL (2020) Assessment of Cu and CuO nanoparticle ecological responses using laboratory small-scale microcosms. Environ Sci: Nano 7:105–115

    CAS  Google Scholar 

  14. Prescott JF, Baggot JD (1993) Antimicrobial Therapy in Veterinary Medicine, 2nd edn. Iowa State University Press, Ames, pp 564–565

    Google Scholar 

  15. Duffy LL, Osmond-McLeod MJ, Judy J, King T (2018) Investigation into the antibacterial activity of silver, zinc oxide and copper oxide nanoparticles against poultry-relevant isolates of Salmonella and Campylobacter. Food Control 92:293–300

    Article  CAS  Google Scholar 

  16. Scott A, Vadalasetty KP, Chwalibog A, Sawosz E (2017) Copper nanoparticles as an alternative feed additive in poultry diet: a review. Nanotechnol Rev 7(1):69–93

    Article  CAS  Google Scholar 

  17. Karlsson HL, Cronholm P, Gustafsson J, Möller L (2008) Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 21:1726–1732. https://doi.org/10.1021/tx800064j

    Article  CAS  PubMed  Google Scholar 

  18. Wang Z, Li N, Zhao J, White JC, Qu P, Xing B (2012) CuO nanoparticle interaction with human epithelial cells: cellular uptake, location, export, and genotoxicity. Chem Res Toxicol 25:1512–1521

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kozłowski K, Jankowski J, Otowski K, Zduńczyk Z, Ognik K (2018) Metabolic parameters in young turkeys fed diets with different inclusion levels of copper nanoparticles. Pol J Vet Sci 21(2):245–253

    PubMed  Google Scholar 

  21. Hassanen EI, Tohamy AF, Hassan AM, Ibrahim MA, Issa MY, Farroh KY (2019a) Pomegranate juice diminishes the mitochondrial-dependent cell death and NF-ĸB signaling pathway induced by copper oxide nanoparticles on the liver and kidneys of rats. Int J Nanomedicine 14:8905–8922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ognik K, Stępniowska A, Cholewińska E, Kozłowski K (2016) The effect of administration of copper nanoparticles to chickens in drinking water on estimated intestinal absorption of iron, zinc, and calcium. Poult Sci 95(9):2045–2051

    Article  CAS  PubMed  Google Scholar 

  23. Timmerman HM, Veldman A, van den Elsen E, Rombouts FM, Beynen AC (2006) Mortality and growth performance of broilers given drinking water supplemented with chicken-pecific probiotics. Poult Sci 85(8):1383–1388

    Article  CAS  PubMed  Google Scholar 

  24. Swayne DE, Glisson JR, Jackwood MW, Pearson JE, Reed WM (1998) A laboratory manual for the isolation and identification of avian pathogens, 4th edn. American Association of Avian Pathologists.Inc., Kennett Square

    Google Scholar 

  25. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351

    Article  CAS  PubMed  Google Scholar 

  26. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/s0076-6879(84)05016-3

  27. Bancroft JD, Gamble M (2013) Theories and practice of histological techniques, 6th edn. Churchil Livingstone, New York

    Google Scholar 

  28. Hassanen EI, Khalaf AA, Tohamy AF, Mohammed ER, Farroh KY (2019b) Toxicopathological and immunological studies on different concentrations of chitosan-coated silver nanoparticles in rats. Int J Nanomedicine 14:4723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hassanen EI, Morsy EM, Hussien AM, Ibrahim MA, Farroh KY (2020) The effect of different concentrations of gold nanoparticles on growth performance, toxicopathological and immunological parameters of broiler chickens. Biosci Rep 40(3):BSR20194296. https://doi.org/10.1042/BSR20194296

  30. Khalaf AA, Hassanen EI, Ibrahim MA, Tohamy AF, Aboseada MA, Hassan HM, Zaki AR (2020) Rosmarinic acid attenuates chromium-induced hepatic and renal oxidative damage and DNA damage in rats. J Biochem Mol Toxicol 34(11):e22579

  31. Ebrahimnia-Bajestan E, Niazmand H, Duangthongsuk W, Wongwises S (2011) Numerical investigation of effective parameters in convective heat transfer of nanofluids flowing under a laminar flow regime. Int J Heat Mass Transf 54(19–20):4376–4388

    Article  CAS  Google Scholar 

  32. Jo MR, Bae SH, Go MR, Kim HJ, Hwang ZG, Choi SJ (2015) Toxicity and biokinetics of colloidal gold nanoparticles. Nanomaterials 5:835–850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Azam A, Ahmed AS, Oves M, Khan MS, Habib SS, Memic A (2012) Antimicrobial activity of metal oxide nanoparticles against gram-positive and gram-negative bacteria: A comparative study. Int J Nanomedicine 7:6003–6009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shahbazi MA, Hamidi M, Makila EM, Zhang H, Almeida PV, Kaasalainen M et al (2013) The mechanisms of surface chemistry effects of mesoporous silicon nanoparticles on immunotoxicity and biocompatibility. Biomaterials 31:7776–7789

    Article  CAS  Google Scholar 

  35. Zhao J, Riediger M (2014) Detecting the oxidative reactivity of nanoparticles: a new protocol for reducing artifacts. J Nanopart Res 16:2493

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Jia HY, Liu Y, Zhang XJ, Han L, Du LB, Tian Q et al (2009) Potential oxidative stress of gold nanoparticles by induced-NO releasing in serum. J Am Chem Soc 131:40–44

    Article  CAS  PubMed  Google Scholar 

  37. Ognik K, Cholewińska E, Czech A, Kozłowski K, Wlazło L, Nowakowicz-Dębek B et al (2016) Effect of silver nanoparticles on the immune, redox, and lipid status of chicken blood. Czech J Anim Sci 61:450–461

    Article  CAS  Google Scholar 

  38. Dang Y, Li Y, Ji Y, Xu L, Tan H, Xu D, Wei Y (2017) Behavior of copper oxide nanoparticles in gastrointestinal juice. 3rd Int Conf Energy Equip Sci Eng IOP Confer Series: Earth Environ Sci 12:828–831

    Google Scholar 

  39. De Jong WH, De Rijk E, Bonetto A et al (2019) Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats. Nanotoxicology 13(1):50–72

    Article  PubMed  CAS  Google Scholar 

  40. Zhang H, Wu X, Mehmood K, Chang Z, Li K, Jiang X, Nabi F, Ijaz M et al (2017) Intestinal epithelial cell injury induced by copper containing nanoparticles in piglets. Environ Toxicol Pharmacol 56:151–156

    Article  CAS  PubMed  Google Scholar 

  41. Xin F (2015) Oxidative Stress Induced by CuO Nanoparticles (CuO NPs) to Human Hepatocarcinoma (HepG2) Cells. J Cancer Ther 6(10):889–895

    Article  CAS  Google Scholar 

  42. Kawanishi S, Inoue S, Yamamoto K (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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  44. Ivask HMA, Blinova I, Dubourguier H, Kahru A (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

    Article  PubMed  CAS  Google Scholar 

  45. Akhtar MJ, Ahamed M, Fareed M, Alrokayan SA, Kumar S (2012) Protective effect of sulphoraphane against oxidative stress mediated toxicity induced by CuO nanoparticles in mouse embryonic fibroblasts BALB 3 T3. J Toxicol Sci 37(1):139–148

    Article  CAS  PubMed  Google Scholar 

  46. Alarifi S, Ali D, Verma A, Alakhtani S, Ali BA (2013) Cytotoxicity and genotoxicity of copper oxide nanoparticles in human skin keratinocytes cells. Int J Toxicol 32(4):296–307

    Article  PubMed  CAS  Google Scholar 

  47. Ahamed M, Siddiquib MA, Akhtar MJ, Ahmad I, Pant AB, Alhadlaq HA (2010) Genotoxic potential of copper oxide nanoparticles in human lung epithelial cells. Biochem Biophys Res Commun 396(2):578–583

    Article  CAS  PubMed  Google Scholar 

  48. Akhtar MJ, Kumar S, Alhadlaq HA, Alrokayan SA, Abu-Salah KM, Ahamed M (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

    Article  CAS  PubMed  Google Scholar 

  49. Piret J-P, Jacques D, Audinot J-N, Mejia J, Boilan E, Noël F et al (2012) Copper (II) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response. Nanoscale 4(22):7168–7184

    Article  CAS  PubMed  Google Scholar 

  50. Gilmour ML, Jaakkola MS, London SJ, Nel AE, Rogers CA (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Khaled A, Moselhy WA, El Hamid MIA, Mahmoud AR, El-Wahab RRA (2019) The effect of aflatoxin B1 contamination on the antioxidant status of broilers’ liver and breast muscle. Adv Animal Vet Sci 7(6):492–497

    Article  Google Scholar 

  52. Lin WS, Xu Y, Huang CC, Ma YF, Shannon KB, Chen DR, Huang YW (2009) Toxicity of nano- and micro-sized ZnO particles in human lung epithelial cells. J Nanopart Res 11:25–39

    Article  CAS  Google Scholar 

  53. Yang H, Liu C, Yang DF, Zhang HS, Xi ZG (2009) Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J Appl Toxicol 29:69–78

    Article  PubMed  CAS  Google Scholar 

  54. ​Khalaf AA, Zaki AR, Galal MK, Ogaly HA, Ibrahim MA, Hassan A, (2017) The potential protective effect of α-lipoic acid against nanocopper particle-induced hepatotoxicity in male rats. Human Exp Toxicol 36(9):881–891

  55. Wang JX, Fan YB, Gao Y, Hu QH, Wang TC (2009) TiO2 nanoparticles translocation and potential toxicological effect in rats after intraarticular injection. Biomaterials 30:4590–4600

    Article  CAS  PubMed  Google Scholar 

  56. Tang J, Xiong L, Wang S, Wang J, Liu L, Li J, Yuanand J, Xi T (2009) Distribution, translocation and accumulation of silver nanoparticles in rats. J Nanosci Nanotechnol 9:4924–4932

    Article  CAS  PubMed  Google Scholar 

  57. Atif Y, Anjum KM, Munir A, Mukhtar H, Khan WA (2018) Evaluation of acute toxicity and effects of sub-acute concentrations of copper oxide nanoparticles (CuO-NPs) on hematology, selected enzymes and histopathology of liver and kidney in Mus musculus. Indian J Animal Res 52(1):92–98

    Google Scholar 

  58. Lee IC, Ko JW, Park SH, Shin NR, Shin IS, Moon C et al (2016) Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats. Int J Nanomedicine 11:2883–2900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Luo YH, Chang LW, Lin P (2015) Metal-based nanoparticles and the immune system: activation, inflammation, and potential applications. BioMed Res Int 2015:143720. https://doi.org/10.1155/2015/143720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Petrarca C, Clemente E, Amato V, Pedata P, Sabbioni E, Bernardini G, Iavicoli I, Cortese S, Niu Q, Otsuki T, Paganelli R, Di Gioacchino M (2015) Engineered metal based nanoparticles and innate immunity. Clin Mol Allergy 13(1):13. https://doi.org/10.1186/s12948-015-0020-1

  61. Najafi-Hajivar S, Zakeri-Milani P, Mohammadi H, Niazi M, Soleymani-Goloujeh M, Baradaran B et al (2016) Overview on experimental models of interactions between nanoparticles and the immune system. Biomed Pharmacother 83:1365–1378

    Article  CAS  PubMed  Google Scholar 

  62. Mantovani A (2010) Molecular pathways linking inflammation and cancer. Curr Mol Med 10:369–373

    Article  CAS  PubMed  Google Scholar 

  63. Ohnmacht C, Pullner A, King SBS, Drexler I, Meier S, Brocker T, Voehringer D (2009) Constitutive ablation of dendritic cells breaks self-tolerance of cd4 t cells and results in spontaneous fatal autoimmunity. J Exp Med 206:549–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank all individuals who participated in the current study.

Funding

This work was supported by the authors.

Author information

Authors and Affiliations

Authors

Contributions

E.I.H. and E.A.M. conceived the study and designed the experiment; A.M.H. and E.I.H. reviewed all the results, carried out data analysis and drafted the manuscript. E.I.H. performed the pathological studies; E.A.M. performed HI test; A.M.H. assessed oxidative stress evaluations; M.A.I. performed the molecular assay and K.Y.F. prepared and characterized CuO-NPs. All authors wrote, read, revised, and approved the final manuscript.

Corresponding author

Correspondence to Marwa A. Ibrahim.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morsy, E.A., Hussien, A.M., Ibrahim, M.A. et al. Cytotoxicity and Genotoxicity of Copper oxide Nanoparticles in chickens. Biol Trace Elem Res 199, 4731–4745 (2021). https://doi.org/10.1007/s12011-021-02595-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-021-02595-4

Keywords

Navigation