Inhibition of Hyperuricemia and Gouty Arthritis in BALB/c Mice Using Copper Oxide Nanoparticles


Nanoparticles are known for their unique properties and are being utilized in various disciplines of sciences. Their nanosize enables them to higher exposure and higher availability when given orally. Gout is an inflammatory disease caused by deposition of monosodium urate (MSU) crystal deposition into the joints. The objective of this study was to evaluate the effects of copper oxide nanoparticles on hyperuricemia and gouty arthritis in mice. In this research, synthesized copper oxide nanoparticles of size ranging from 30 to 50 nm were administered orally to mice having gouty arthritis and hyperuricemia. Various biochemical markers were conducted to determine the effects of copper oxide nanoparticles. It was observed that the mice treated with CuO NPs at various concentrations showed a significant (0.001) decrease in the serum uric acid levels in comparison with the negative control. Furthermore, creatinine levels were also normal in comparison with the control mice. Measurement of synovial joints also revealed that mice administered with CuO NPs had reduced inflammation of synovial joints in comparison with the negative control. From this research, it was concluded that copper oxide nanoparticles have potential in the treatment of hyperuricemia and gouty arthritis by decreasing serum uric acid and inflammation in synovial joints.

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

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Kuo C-F, Grainge MJ, Zhang W, Doherty M (2015) Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol 11(11):649–662

    Article  Google Scholar 

  2. 2.

    Roddy E, Doherty M (2010) Gout. Epidemiology of gout. Arthritis Res Ther 12(6):223

    Article  Google Scholar 

  3. 3.

    Schauer C, Janko C, Munoz LE, Zhao Y, Kienhöfer D, Frey B, Lell M, Manger B, Rech J, Naschberger E, Holmdahl R, Krenn V, Harrer T, Jeremic I, Bilyy R, Schett G, Hoffmann M, Herrmann M (2014) Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med 20(5):511–517

    CAS  Article  Google Scholar 

  4. 4.

    Mitroulis I, Kambas K, Chrysanthopoulou A, Skendros P, Apostolidou E, Kourtzelis I, Drosos GI, Boumpas DT, Ritis K (2011) Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout. PLoS One 6(12):e29318

    CAS  Article  Google Scholar 

  5. 5.

    Mitroulis I, Kambas K, Ritis K (2013) Neutrophils, IL-1β, and gout: is there a link? Semin Immunopathol 35(4):501–512

    CAS  Article  Google Scholar 

  6. 6.

    So A (2013) How to regulate neutrophils in gout. Arthritis Res Ther 15:118

    Article  Google Scholar 

  7. 7.

    So A (2008) Developments in the scientific and clinical understanding of gout. Arthritis Res Ther 10(5):221

    Article  Google Scholar 

  8. 8.

    Busso N, Ea H-K (2011) The mechanisms of inflammation in gout and pseudogout (CPP-induced arthritis). Reumatismo 63(4):230–237

    Google Scholar 

  9. 9.

    Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440(7081):237–241

    CAS  Article  Google Scholar 

  10. 10.

    Pétrilli V, Martinon F (2007) The inflammasome, autoinflammatory diseases, and gout. Joint Bone Spine 74(6):571–576

    Article  Google Scholar 

  11. 11.

    Oliveira S, Canetti C, Ribeiro R, Cunha F (2008) Neutrophil migration induced by IL-1Î2 depends upon LTB 4 released by macrophages and upon TNF-α and IL-1Î2 released by mast cells. Inflammation 31(1):36–46

    CAS  Article  Google Scholar 

  12. 12.

    Brinkmann V, Zychlinsky A (2012) Neutrophil extracellular traps: is immunity the second function of chromatin? J Cell Biol 198(5):773–783

    CAS  Article  Google Scholar 

  13. 13.

    Grayson PC, Kaplan MJ (2016) At the bench: neutrophil extracellular traps (NETs) highlight novel aspects of innate immune system involvement in autoimmune diseases. J Leukoc Biol 99(2):253–264

    CAS  Article  Google Scholar 

  14. 14.

    Abbott KC, Kimmel PL, Dharnidharka V, Oglesby RJ, Agodoa LY, Caillard S (2005) New-onset gout after kidney transplantation: incidence, risk factors and implications. Transplantation 80(10):1383–1391

    Article  Google Scholar 

  15. 15.

    Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A (2007) Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 176(2):231–241

    CAS  Article  Google Scholar 

  16. 16.

    Stoiber W, Obermayer A, Steinbacher P, Krautgartner W-D (2015) The role of reactive oxygen species (ROS) in the formation of extracellular traps (ETs) in humans. Biomolecules 5(2):702–723

    CAS  Article  Google Scholar 

  17. 17.

    Wang J, Arase H (2014) Regulation of immune responses by neutrophils. Ann N Y Acad Sci 1319(1):66–81

    CAS  Article  Google Scholar 

  18. 18.

    Lin S, Zeng L, Zhang G, Liao Y, Gong D (2017) Synthesis, characterization and xanthine oxidase inhibition of Cu (II)–chrysin complex. Spectrochim Acta A Mol Biomol Spectrosc 178:71–78

    CAS  Article  Google Scholar 

  19. 19.

    Konstantinova SG, Russanova IE, Russanov EM (1991) Do the copper complexes of histamine, histidine and of two H2-antagonists react with O−2? Free Radic Res Commun 12(1):215–220

    Article  Google Scholar 

  20. 20.

    Aruoja V, Dubourguier H-C, Kasemets K, Kahru A (2009) Toxicity of nanoparticles of CuO, ZnO and TiO2 to microalgae Pseudokirchneriella subcapitata. Sci Total Environ 407(4):1461–1468

    CAS  Article  Google Scholar 

  21. 21.

    Wang H, Huang Y, Tan Z, Hu X (2004) Fabrication and characterization of copper nanoparticle thin-films and the electrocatalytic behavior. Anal Chim Acta 526(1):13–17

    CAS  Article  Google Scholar 

  22. 22.

    Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR (2014) Modern nutrition in health and disease, 11 edn. Lippincott Williams &Wilkins

  23. 23.

    Li L-Z, Zhou G-X, Li J, Jiang W, Liu B-L, Zhou W (2018) Compounds containing trace element copper or zinc exhibit as potent hyperuricemia inhibitors via xanthine oxidase inactivation. J Trace Elem Med Biol 49:72–78

    CAS  Article  Google Scholar 

  24. 24.

    Khan A, Rashid A, Younas R, Chong R (2016) A chemical reduction approach to the synthesis of copper nanoparticles. Int Nano Lett 6(1):21–26

    CAS  Article  Google Scholar 

  25. 25.

    Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet

  26. 26.

    Razavian MH, Masaimanesh M (2014) Ingestion of silver nanoparticles leads to changes in blood parameters. Nanomed J 1(5):339–345

    Google Scholar 

  27. 27.

    Hébert CD, Elwell MR, Travlos GS, Fitz CJ, Bucher JR (1993) Subchronic toxicity of cupric sulfate administered in drinking water and feed to rats and mice. Fundam Appl Toxicol 21(4):461–475

    Article  Google Scholar 

  28. 28.

    Nishimura A, Akahoshi T, Takahashi M, Takagishi K, Itoman M, Kondo H, Takahashi Y, Yokoi K, Mukaida N, Matsushima K (1997) Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8. J Leukoc Biol 62(4):444–449

    CAS  Article  Google Scholar 

  29. 29.

    Tiwari S, Dwivedi H, Kymonil KM, Saraf SA (2015) Urate crystal degradation for treatment of gout: a nanoparticulate combination therapy approach. Drug Deliv Transl Res 5(3):219–230

    CAS  Article  Google Scholar 

  30. 30.

    Jang EM, Choi MS, Jung UJ, Kim MJ, Kim HJ, Jeon SM, Shin SK, Seong CN, Lee MK (2008) Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat–fed hamsters. Metabolism 57(11):1576–1583

    CAS  Article  Google Scholar 

  31. 31.

    Lee IC, Ko JW, Park SH, Shin NR, Shin IS, Moon C, Kim JH, Kim HC, Kim JC (2016) Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles. Particle Fibre Toxicol 13(1):56

    Article  Google Scholar 

Download references


This manuscript is a part of the doctoral dissertation of Mubin Mustafa. The authors are thankful to International Islamic, Riphah International University, Islamabad, Pakistan, and National University of Science and Technology, Islamabad, Pakistan, for providing research facilities.

Author information



Corresponding author

Correspondence to Mubin Mustafa Kiyani.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kiyani, M.M., Rehman, H., Hussain, M.A. et al. Inhibition of Hyperuricemia and Gouty Arthritis in BALB/c Mice Using Copper Oxide Nanoparticles. Biol Trace Elem Res 193, 494–501 (2020).

Download citation


  • Copper oxide
  • Nanoparticles
  • Gouty arthritis
  • Hyperuricemia
  • Uric acid
  • Synovial joints