Skip to main content
SpringerLink
Log in

Effect of dietary copper nanoparticles versus one copper (II) salt: Analysis of vasoreactivity in a rat model

  • Original article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Vascular defects in the mechanical properties of aorta and muscular arteries have been previously reported in animals with copper-deficient feed. However, the interaction between copper nanoparticles (CuNPs) and mechanical properties of arteries has not been reported. Hence, the present study was aimed to evaluate the effect of copper nanoparticles on the vasoreactivity of rat isolated thoracic arteries.

Methods

In this study, 5 week old male Wistar rats were fed a copper-adequate diet (CuA, 6.5 mg copper/kg diet), copper-deficient diet (CuD) and copper-modified diets, enriched with copper as a salt (CuS) and as copper nanoparticles (CuNPs) of 40–60 nm in diameter.

Results

There was a strong relationship between CuNPs and CuS administration in the tensile strength of the thoracic aorta subjected to phenylephrine treatment in the concentration range of 10−7–10−5 M. This was also seen between CuNPs and the control diet in the same concentration ranges. In addition vasodilation induced by acetylcholine at the concentration range of 10−7–10−5 M was significantly reduced in CuD and NPs feed animals. In CuNPs fed rats, activities of Cu,Zn-SOD, CAT and copper concentration in cardiomyocytes were not influenced when compared with CuS control. In contrast, in CuS-low diet the activities of studied enzymes and copper concentration were pointing towards copper deficiency.

Conclusions

Our results demonstrate for the first time that the observed effects of copper administration in the form of NPs are attributed mainly to the NPs rather than copper itself. Thus another mechanism not related with Cu,Zn-SOD and CAT seems to be involved.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CAT:

catalase

CuA:

copper-adequate diet

CuD:

copper-deficient diet

CuNPs:

copper-nanoparticle diet

CuS:

CuCO3 fed rats

MMX:

mineral matrix

NO:

nitric oxide

O2−:

superoxide anion

ROS:

reactive oxygen species

SOD:

superoxide dismutase

References

  1. Saari JT. Copper deficiency and cardiovascular disease:role of peroxidation, glycation, and nitration. Can J Physiol Pharmacol 2000;78:848–55.

    Article  CAS  Google Scholar 

  2. Li Y, Wang L, Schuschke DA, Zhou Z, Saari JT, Kang YJ. Marginal dietary copper restriction induces cardiomyopathy in rats. J Nutr 2005;135:2130–6.

    Article  CAS  Google Scholar 

  3. Bergomi M, Rovesti S, Vinceti M, Caselgrandi E, Vivoli G. Zinc and copper status and blood pressure. J Trace Elem Med Biol 1997;11:166–9.

    Article  CAS  Google Scholar 

  4. Carlström M, Lai EY, Steege A, Sendeski M, Ma Z, Zabihi S, et al. Nitric oxide deficiency and increased adenosine response of afferent arterioles in hydronephrotic mice with hypertension. Hypertension 2008;51:1386–92.

    Article  Google Scholar 

  5. Vivoli G, Bergomi M, Rovesti S, Pinotti M, Caselgrandi E. Zinc, copper, and zincor copper-dependent enzymes in human hypertension. Biol Trace Elem Res 1995;49:97–106.

    Article  CAS  Google Scholar 

  6. Majewski M, Kozlowska A, Thoene M, Lepiarczyk E, Grzegorzewski WJ. Overview of the role of vitamins and minerals on the kynurenine pathway in health and disease. J Physiol Pharmacol 2016;67:3–19.

    CAS  PubMed  Google Scholar 

  7. Matthys KE, Van Hove CE, Kockx MM, Andries LJ, Van Osselaer N, Herman AG, et al. Exposure to oxidized low-density lipoprotein in vivo enhances intimal thickening and selectively impairs endothelium-dependent dilation in the rabbit. Cardiovasc Res 1998;37:239–46.

    Article  CAS  Google Scholar 

  8. Schuschke DA. Dietary copper in the physiology of the microcirculation. J Nutr 1997;127:2274–81.

    Article  CAS  Google Scholar 

  9. Schuschke DA, Saari JT, Miller FN. Arteriolar dilation to endotoxin is increased in copper-deficient rats. Inflammation 1997;21:45–53.

    Article  CAS  Google Scholar 

  10. Cohen NL, Keen CL, Hurley LS, Lönnerdal B. Determinants of copper-deficiency anemia in rats. J Nutr 1985;115:710–25.

    Article  CAS  Google Scholar 

  11. Schuschke DA, Falcone JC, Saari JT, Fleming JT, Percival SS, Young SA, et al. Endothelial cell calcium mobilization to acetylcholine is attenuated in copper-deficient rats. Endothelium 1999;7:83–92.

    Article  Google Scholar 

  12. Schuschke DA, Percival SS, Saari JT, Miller FN. Relationship between dietary copper concentration and acetylcholine- induced vasodilation in the microcirculation of rats. Biofactors 1999;10:321–7.

    Article  CAS  Google Scholar 

  13. Spinazzi M, Sghirlanzoni A, Salviati L, Angelini C. Impaired copper and iron metabolism in blood cells and muscles of patients affected by copper deficiency myeloneuropathy. Neuropathol Appl Neurobiol 2014;40:888–98.

    Article  CAS  Google Scholar 

  14. Al-Bayati MA, Jamil DA, Al-Aubaidy HA. Cardiovascular effects of copper deficiency on activity of superoxide dismutase in diabetic nephropathy. N Am J Med Sci 2015;7:41–6.

    Article  Google Scholar 

  15. Urso E, Maffia M. Behind the link between copper and angiogenesis:established mechanisms and an overview on the role of vascular copper transport systems. J Vasc Res 2015;52:172–96.

    Article  CAS  Google Scholar 

  16. Dalle Lucca JJ, Saari JT, Falcone JC, Schuschke DA. Neointima formation in the rat carotid artery is exacerbated by dietary copper deficiency. Exp Biol Med 2002;227:487–91.

    Article  CAS  Google Scholar 

  17. Klevay LM. Cardiovascular disease from copper deficiency-a history. J Nutr 2000;130:489–92.

    Article  Google Scholar 

  18. Kang YJ. Copper and homocysteine in cardiovascular diseases. Pharmacol Ther 2011;129:321–31.

    Article  CAS  Google Scholar 

  19. Prohaska JR, Heller LJ. Calcium reintroduction decreases viability of cardiac myocytes from copper-deficient rats. J Nutr 1999;129:1842–5.

    Article  CAS  Google Scholar 

  20. Falcone JC, Saari JT, Kang YJ, Schuschke DA. Vasoreactivity in an adult rat model of marginal copper deficiency. Nutr Res 2005;25:177–86.

    Article  CAS  Google Scholar 

  21. Wang YC, Hu CW, Liu MY, Jiang HC, Huo R, Dong DL. Copper induces vasodilation and antagonizes noradrenaline — Induced vasoconstriction in rat mesenteric artery. Cell Physiol Biochem 2013;32:1247–54.

    Article  CAS  Google Scholar 

  22. Yan M, Liu DL, Chua YL, Chen C, Lim YL. Effects of micromolar concentrations of manganese, copper, and zinc on α1 -adrenoceptor-mediating contraction in rat aorta. Biol Trace Elem Res 2001;82:159–66.

    Article  CAS  Google Scholar 

  23. Kitano S. Membrane and contractile properties of rat vascular tissue in copper-deficient conditions. Circ Res 1980;46:681–9.

    Article  CAS  Google Scholar 

  24. Ramyadevi J, Jeyasubramanian K, Marikani A, Rajakumar G, Rahuman AA. Synthesis and antimicrobial activity of copper NPs. Mater Lett 2012;71:114–6.

    Article  CAS  Google Scholar 

  25. Gomes SI, Novais SC, Gravato C, Guilhermino L, Scott-Fordsmand JJ, Soares AM, et al. Effect of Cu-NPs versus one Cu-salt:analysis of stress biomarkers response in Enchytraeus albidus (Oligochaeta). Nanotoxicology 2012;6:134–43.

    Article  CAS  Google Scholar 

  26. Xu P, Xu J, Liu S, Ren G, Yang Z. In vitro toxicity of nanosized copper particles in PC12 cells induced by oxidative stress. J Nanopart Res 2012;14:906, doi:https://doi.org/10.1007/s11051-012-0906-5.

    Article  Google Scholar 

  27. Xu P, Xu J, Liu S, Yang Z. Nano copper induced apoptosis in podocytes via increasing oxidative stress. J Hazard Mater 2012;30:279–86.

    Article  Google Scholar 

  28. Xu P, Li Z, Zhang X, Yang Z. Increased response to oxidative stress challenge of nano-copper-induced apoptosis in mesangial cells. J Nanopart Res 2014;16, doi:https://doi.org/10.1007/s11051-014-2777-4.

  29. Merrifield DL, Shaw BJ, Harper GM, Saoud IP, Davies SJ, Handy RD, et al. Ingestion of metal-nanoparticle contaminated food disrupts endogenous microbiota in zebrafish (Danio rerio). Environ Pollut 2013;174:157–63.

    Article  CAS  Google Scholar 

  30. Handy RD, Al-Bairuty G, Al-Jubory A, Ramsden CS, Boyle D, Shaw BJ, et al. Effects of manufactured nanomaterials on fishes:a target organ and body systems physiology approach. J Fish Biol 2011;79:821–53.

    Article  CAS  Google Scholar 

  31. Prabhu BM, Ali SF, Murdock RC, Hussain SM, Srivatsan M. Copper NPs exert size and concentration dependent toxicity on somatosensory neurons of rat. Nanotoxicology 2010;4:150–60.

    Article  CAS  Google Scholar 

  32. Lei R, Wu C, Yang B, Ma H, Shi C, Wang Q, et al. Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats:a rapid in vivo screening method for nanotoxicity. Toxicol Appl Pharmacol 2008;232:292–301.

    Article  CAS  Google Scholar 

  33. Misra HP, Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170–5.

    CAS  Google Scholar 

  34. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121–6.

    Article  CAS  Google Scholar 

  35. Gobejishvili L, Saari J, Adeagbo A, Zhang X, Schuschke D. Dietary copper deficiency increases inducible nitric oxide synthase-mediated vascular dilation in rat aorta. J Trace Elem Exp Med 2002;15:85–95.

    Article  CAS  Google Scholar 

  36. Schuschke DA, Reed MW, Saari JT, Miller FN. Copper deficiency alters vasodilation in the rat cremaster muscle microcirculation. J Nutr 1992;122:1547–52.

    Article  CAS  Google Scholar 

  37. Chiarugi A, Pitari GM, Costa R, Ferrante M, Villari L, Amico-Roxas M, et al. Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta. Br J Pharmacol 2002;136:1185–93.

    Article  CAS  Google Scholar 

  38. Reyes VC, Spitzmiller MR, Hong-Hermesdorf A, Kropat J, Damoiseaux RD, Merchant SS, et al. Copper status of exposed microorganisms influences susceptibility to metallic NPs. Environ Toxicol Chem 2016;35:1148–58.

    Article  CAS  Google Scholar 

  39. 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;290:208–17.

    Article  Google Scholar 

  40. Song L, Connolly M, Fernández-Cruz ML, Vijver MG, Fernández M, Conde E, et al. Species-specific toxicity of copper NPs among mammalian and piscine cell lines. Nanotoxicology 2014;8:383–93.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland

    Michal Majewski

  2. Department of Biochemistry and Toxicology, Faculty of Biology, Animal Sciences and Bioeconomy, University of Life Sciences, Lublin, Poland

    Katarzyna Ognik

  3. Division of Food Science, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Olsztyn, Poland

    Przemyslaw Zdunczyk & Jerzy Juskiewicz

Authors
  1. Michal Majewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katarzyna Ognik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Przemyslaw Zdunczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jerzy Juskiewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michal Majewski.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Majewski, M., Ognik, K., Zdunczyk, P. et al. Effect of dietary copper nanoparticles versus one copper (II) salt: Analysis of vasoreactivity in a rat model. Pharmacol. Rep 69, 1282–1288 (2017). https://doi.org/10.1016/j.pharep.2017.06.001

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2017.06.001

Keywords

Search

Navigation