The acute liver injury in rat caused by gold nanoparticles

Document Type: Research Paper

Authors

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

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

10.7508/nmj.2015.04.005

Abstract

Objective(s):  
Gold nanoparticles (GNPs) command a great deal of attention for biomedical applications nowadays. The data about the degree of toxicity and the accumulation of gold nanoparticles in-vivo is not enough to judge. 
Materials and Methods: 
A total of 32 healthy male Wistar rats were randomly divided into 4 including: three GNP-treated and one control group. Groups 1, 2 and 3 received 0.5 cc of a solution containing 5, 10, and 100 ppm Au daily via intraperitoneal (IP) injection for 7 days, respectively. The control group was treated with 0.5 cc normal saline with same procedure. Then, several biochemical parameters such as serum glutamate oxaloacetat transaminase (SGOT) and serum glutamate pyrvate transaminase (SGPT) were evaluated at 2, 7 and 14 days after the last injection. After 14 days, all the rats were sacrificed and liver, lung tissues were separated and evaluated. 
Results:  
SGOT two days after intervention was significantly greater in the group 2 than the control group. In liver histological assessment, in group 1, basophils were observed around the central veins, in group 2 fading and no observation of central veins was seen, and in group 3 hepatic damage was noticed. The lung histological results showed severe vascular hyperemia in group 1, air sacs damage in group 2, and complete air sacs destruction in group 3. 
Conclusion: 
The results showed extreme changes in the histopathology of lung and liver tissues caused by spherical nanogold with 5-10 nm size in all of three treatment groups.

Keywords


1. Manikandan J, Ong CN, Yu LE, Ong WY.Biodistribution of gold nanoparticles and gene expression changes in the liver and spleen after intravenous administration in rats. Biomaterials. 2010; 31(8):2034-2042.

2. AlkilanyAM, Murphy CJ.Toxity and cellular uptake of gold nanoparticles: What we have learned so far? J Nanopart Res. 2010; 12(7): 2313-2333.

3. Shanei A,Sazgarnia A, TayyebiMeibodi N, Eshghi H, Hassanzadeh-Khayyat M, Esmaily H, et al. Sonodynamic therapy using protoporphyrin IX conjugated to gold nanoparticles: an in vivo study on a colon tumor model. Iran J Basic Med Sci. 2012; 15(2): 759-767.

4. Studer AM, Limbach LK, Van Duc L, Krumeich F, Athanassiou EK, Gerber LC, et al.Nanoparticle cytotoxicity depends on intracellular solubility:comparison of stabilized copper metal and degradable copper oxide nanoparticles. Toxicol Lett. 2010; 197(3):169-174.

5. Gunawan C, Teoh WY, Marquis CP, Amal R.Cytotoxic origin of copper(II) oxide nanoparticles: comparative studies with micron-sized particles,leachate and metal salts. ACS Nano. 2011; 5(9):7214-7225.

6. ChenYSh, Hung YCh, Liau I, Huang, GS. Assessment of the invivo toxicity of gold nanoparticles. Nanoscale Res Lett. 2009; 4(8): 858-864.

7. Cho WS, Cho MJ,Jeong J ET AL.Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles. ToxicolApplPharmacol. 2009; 236(1):16-24.

8. De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJ, Geertsma RE.Particle size-dependent organ distribution of gold nanoparticles after intravenous administration.Biomaterials. 2008; 29(12):1912-1919.

9. Choi SY, Jeong S, Jang SH, Park J, Park JH, Ock KS, et al. In vitro toxicity of serum protein-adsorbed citrate-reduced gold nanoparticles in human lung adenocarcinoma cells. ToxicolIn Vitro. 2012; 26(2):229-237.

10. Trickler WJ, Lantz SM, Murdock RC, Schrand AM, Robinson BL, Newport GD, et al. Brain microvessel endothelial cells responses to gold nanoparticles: In vitro pro-inflammatory mediators and permeability. Nanotoxicology. 2011; 5(4):479-492.

11. Li JJ, Lo SL, Ng CT, Gurung RL, Hartono D, Hande MP, et al. Genomic instability of gold nanoparticle treated human lung fibroblast cells. Biomaterials. 2011;32(23):5515-5523.

12. Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. Small. 2008; 4(1):26-49.

13. Colvin, V. The Potential environmental impact of engineered nanomaterials. Nat Biotechnol. 2003; 21: 1166-1170.

14. Shukla R, Bansal V, Chaudhary M, Basu A, Bhonde RR, Sastry M. Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. Langmuir. 2005; 21(23): 10644-10654.

15. Takahashi H, Niidome Y, Niidome T, Kaneko K, Kawasak H, Yamada S. Modification of gold nanorods using phosphatidylcholine to reduce cytotoxicity. Langmuir. 2006; 22(1): 2-5.

16. Pan Y, Neuss S, Leifert A, Fischler M, Wen F, Simon U, et al. Size-dependent cytotoxicity of gold nanoparticles. Small. 2007; 3(11): 1941-1949.

17. TerentyuklGS,Maslyakova GN, Suleymanova LV, KhlebtsovBN, Kogan BY,Akchurin GG, et al. Circulation and distribution of gold nanoparticles and induced alterations of tissue morphology at intravenous particle delivery. J Biophotonics. 2009; 2(5): 292-302.

18. Sonavane G, Tomoda K, Makino K.Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size. Colloids Surf B Biointerfaces. 2008; 66(2): 274-280.

19. Sadauskas E, Danscher G, Stoltenberg M, Vogel U, Larsen A, Wallin H. Protracted elimination of gold nanoparticles from mouse liver. Nanomedicine. 2009; 5(2): 162-169.

20. Aggarwal P, Hall JB, McLeland CB,Dobrovolskaia MA, McNeil SE. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev. 2009; 61(6): 428-437.

21. Lanone S, Boczkowski J. Biomedical applications and potential health risks of nanomaterials: molecular mechanisms. CurrMol Med. 2006; 6(6): 651-663.

22. Hillyer JF, Albrecht RM. Correlative instrumental neutron activation analysis, light microscopy, transmission electron microscopy, and X-ray microanalysis for qualitative and quantitative detection of colloidal gold spheres in biological specimens.MicroscMicroanal. 1999; 4(5): 481-490.

23. Niidome T, Yamagata M, Okamoto Y, Akiyama Y, Takahashi H, Kawano T, et al. PEG-modified gold nanorods with a stealth character for in vivo application. J Control Release. 2006; 114(3): 343-347.

24. Abdelhalim MAK, Jarrar BM. Gold nanoparticles administration induced prominent inflammatory, central vein intima disruption, fatty change and Kupffer cells hyperplasia. Lipids Health Dis.2011; 10: 133.

25. Abdelhalim MAK, Jarrar BM. Gold nanoparticles induced cloudy swelling to hydropic degeneration, cytoplasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis in the liver. Lipids Health Dis.2011; 10: 166.

26. Abdelhalim MAK, Jarrar BM. Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles. Lipids Health Dis. 2011; 10: 163.

27. Abdelhalim MAK, Jarrar BM. The appearance of renal cells cytoplasmic degeneration and nuclear destruction might be an indication of GNPs toxicity. Lipids Health Dis.2011; 10: 147.

28. Abdelhalim MAK. Exposure to gold nanoparticles produces cardiac tissue damage that depends on the size and duration of exposure. Lipids Health Dis.2011; 10: 205.

29. Abdelhalim MAK. Exposure to gold nanoparticles produces pneumonia, fibrosis, chronic inflammatory cell infiltrates, congested and dilated blood vessels, and hemosiderin granule and emphysema foci. J Cancer SciTher.2012; 4(3): 046-050.

30. Abdelhalim MAK. Gold nanoparticles administration induces disarray of heart muscle, hemorrhagic, chronic inflammatory cells infiltrated by small lymphocytes, cytoplasmic vacuolization and congested and dilated blood vessels. Lipids Health Dis. 2011; 10: 233.

31. Abdelhalim MAK. Optimizing a novel method for synthesizing gold nanoparticles: biophysical studies. J Cancer SciTher. 2012; 4: 140-143.

32. Oberdِrster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H. Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol. 2005; 2:8.

33. Damabach DM,Andrews BA,Moulin F. New technologies and screeninig strategies for hepatotoxicity: use of invitro models.ToxicolPathol. 2005; 33(1):17-26.