Acute effect of nano-copper on liver tissue and function in rat


1 Department of Microbiology, Falavarjan Branch, Islamic Azad University, Isfahan, Iran

2 Department of Biology, Izeh Branch, Islamic Azad University, Izeh, Iran



This paper reports on the toxicity of CuO NPs on hepatic enzymes and liver and lung histology.

Materials and Methods:
To assess the toxicity of copper nanoparticles (10-15 nm) in vivo, pathological examinations and blood biochemical indexes including serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) at various time points (2, 7 and 14 days)were studied. Thirty two Wistar rats were randomly divided into four groups. Treatment groups (group 1, 2, 3) received CuO NP solution containing 5, 10 and 100 mg/kg, respectively. Control group received 0.5 mL of normal saline via ip injection for 7 consecutive days. After 14 days, the tissue of liver and lung were collected and investigated for their histological problems.
The histology of the hepatic tissues showed vasculature in central veins and portal triad vessels in all three treatment groups. Histology of lungs showed air sac wall thickening and increased fibrous tissue in all three groups. Biochemical results of the hepatic enzymes showed that the SGOT levels in groups 1 and 2 were significantly higher than the control group two days after the intervention.
Results of this study indicated that all concentration of copper nanoparticles [with 10-15 nm diameters, spherical shape, purity of 99.9%, mineral in nature, and wet synthesis method in liquid phase (alternation)] induce toxicity and changes of histo-pathological changes in liver and lung tissues of rats. It is evident that these nanoparticles cannot be used for human purposes because of their toxicity.


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

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

3.Ruparelia JP, Chatterjee AK, Duttagupta, SP, Mukherji S. Strain specificity in antimicrobial activity of silver and copper nanoparticles. Acta Biomater. 4(3) :707-716.

4.Kim JS, Adamcakova-Dodd A, O’Shaughnessy PT, Grassian VH, Thorne PS. Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model. Part Fibre Toxicol. 2011; 8:29. doi: 10.1186/1743-8977-8-29.

5.Karlsson HL, Cronholm P, Gustafsson J, Moller L. Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol. 2008; 21(9): 1726-1732.

6.Jones CF, Grainger DW. In vitro assessments of nanomaterial toxicity. Adv Drug Deliv Rev. 2009; 1: 438-456.

7.Landsiedel R, Kapp MD, Schulz M, Wiench K, Oesch F. Genotoxicity investigations on nanomaterials: methods, preparation and characterization of test material, potential artifacts and limitations--many questions, some answers. Mutat Res. 2009; 681(2-3): 241-258.

8.Møller P, Jacobsen NR, Folkmann JK, Danielsen PH, Mikkelsen L, Hemmingsen JG, et al. Role of oxidative damage in toxicity of particulates. Free Radic Res. 2010; 44(1): 1-46.

9.Oberdörster G, Stone V, Donaldson K. Toxicology of nanoparticles: a historical perspective. Nanotoxicology. 2007; 1(1): 2-25.

10.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): 1726-1732.

11.Karlsson HL, Gustafsson J, Cronholm P, Möller L. Size-dependent toxicity of metal oxide particles--a comparison between nano- and micrometer size. Toxicol Lett. 2009; 188(2): 112-118.

12.Chaves SB, Lacava LM, Lacava ZGM. Light microscopy and magnetic  resonance characterization of a DSMA-coated magnetic fluid in mice. IEEE Transactions on magnetic. 2002; 38(5): 3231-3233.

13.Liu G, Li X, Qin B, Xing D, Guo Y, Fan R. Investigation of the mending effect and mechanism of copper nanoparticles on a tribologically stressed surface. Tribol Lett. 2004; 17(4): 961-966.

14.N. N. Glushchenko, I. P. Olkhovskaya, T. V. Pleteneva, L. D. Fatkullina, Yu. A. Ershov and Yu. I. Fedorov.  The Biological Effect of Superfine Metal Powders. Izvestiya АN. 1989; 3: 415-418.

15.Sizova EA, Miroshnikov SA, Polyakova VS, Natalia Gluschenko, Anatoly Skalny. Copper nanoparticles as modulators of apoptosis and structural changes in tissues. J Biomater Nanobiotechnol. 2012; 3: 97-104.

16.Chen Z, Meng H, Xing G, Chen C, Zhao Y, Jia G, et al. Acute toxicological effects of copper nanoparticles in vivo. Toxicol Lett. 2006; 163(2): 109-120.

17.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(2): 292-301.

18.Murray AR, Kisin E, Leonard SS, Young SH, Kommineni C, Kagan VE, et al. Oxidative stress and inflammatory response in dermal toxicity  of single-walled carbon nanotubes. Toxicology.2009; 257(3):161-171.

 19.G. G. Onishchenko. The Concept of Toxicological Studies, Estimated Risk Methodology, Methods of Identification and Quantification of Nanomaterials. Resolution 79, Registered in the Russian Ministry of Justice, Registration. 2007; 10528.

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

21.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; 18; 290(2-3): 208-217.

22.Ju-Nam Y, Lead JR. Manufactured n