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Orally administered gold nanoparticles caused mild oxidative stress in the lungs and liver of Wistar rats

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Abstract

Gold nanoparticles (AuNPs) are increasingly being used in real clinical settings for drug delivery, gene transfer, cancer cell detection, phototherapy, and antiviral and anti-inflammatory activities, among other uses. Hence, knowledge about their potential toxicity and health impact is essential. This study therefore investigated the biochemical effects of gold nanoparticles in Wistar rats. Sixteen (16) Wistar rats were grouped into 4 (n = 4). Animals in the negative control group were orally administered 0.3 ml of distilled water (vehicle) while other treatment groups were respectively given oral administration of 0.3 ml each of 1, 10, and 20 mg/kg b.w. AuNPs for 7 days. Biochemical measurements of oxidative stress indices in rat plasma and tissue homogenates were recorded on a UV/Vis spectrophotometer. There was no significant (p > 0.05) difference in the plasma and brain for all the biochemical parameters measured, when compared with the negative control group. Conversely, AuNPs at 20 mg/kg b.w. significantly (p < 0.001) raised protein carbonyl and lipid peroxidation levels in the lungs and percentage (%) DNA fragmented levels in the liver (p < 0.05). These results indicate that AuNPs particularly at 20 mg/kg b.w. might predispose to oxidative stress.

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References

  • Abdelhalim MAK (2012) Exposure to gold nanoparticles produces pneumonia, fibrosis, chronic inflammatory cell infiltrates, congested and dilated blood vessels, and hemosiderin granule and emphysema foci. J Cancer Sci Ther 4(3):46–50. https://doi.org/10.4172/1948-5956.1000109

    Article  CAS  Google Scholar 

  • Adeyemi OS, Whiteley CG (2013) Interaction of nanoparticles with arginine kinase from Trypanosoma brucei: kinetic and mechanistic evaluation. Int J Biol Macromol 62:450–456. https://doi.org/10.1016/j.ijbiomac.2013.09.008

    Article  CAS  PubMed  Google Scholar 

  • Adeyemi OS, Murata Y, Sugi T, Kato K (2017) Inorganic nanoparticles kill Toxoplasma gondii via changes in redox status. Int J Nanomedicine 12:1647–1661

    Article  Google Scholar 

  • Adeyemi OS, Molefe NI, Awakan OJ, Nwonuma CO, Alejolowo OO, Olaolu T, Maimako RF, Suganuma K, Han Y, Kato K (2018) Metal nanoparticles restrict the growth of protozoan parasite. Artif Cells Nanomed Biotechnol 46(53):586–594. https://doi.org/10.1080/21691401.2018.1489267

    Article  CAS  Google Scholar 

  • Aksenov MY, Aksenova MV, Mrkesbery WR, Butterfield DA (1998) Amyloid β-peptide (1-40) mediated oxidative stress in cultured hippocampal neurons. J Mol Nerosci 10:181–192

    Article  CAS  Google Scholar 

  • Bednarski M, Dudek M, Knutelska J, Nowin L, Sapa J, Zygmunt M, Nowak G, Luty-Błocho M, Wojnicki M, Fitzner K, Tesiorowski M (2015) The influence of the route of administration of gold nanoparticles on their tissue distribution and basic biochemical parameters: in vivo studies. Pharmacol Rep 67:405–409

    Article  CAS  Google Scholar 

  • Card JW, Zeldin DC, Bonner JC, Nestmann ER (2008) Pulmonary applications and toxicity of engineered nanoparticles. Am J Phys Lung Cell Mol Phys 295(3):L400–L411

    CAS  Google Scholar 

  • Castegna A, Drake J, Pocernich C, Butterfield DA (2003) Protein carbonyl levels - An assessment of protein oxidation. In: Methods in Phamacology and Toxicology: Methods in Biological Oxidative Stress, Eds. K Hensley and RA Floyd. Humana Press Inc., Totowa, pp 161–166

  • Chance B, Maehly AC (1955) Assay of catalase and peroxidases. Methods Enzymol 2:773–775

    Google Scholar 

  • Cho WS, Cho M, Jeong J, Choi M, Cho HY, Han BS, Kim SH, Kim HO, Lim YT, Chung BH, Jeong J (2009) Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles. Toxicol Appl Pharmacol 236(1):16–24. https://doi.org/10.1016/j.taap.2008.12.023

    Article  CAS  PubMed  Google Scholar 

  • Connor E, Mwamuka J, Gole A, Murphy C, Wyatt M (2005) Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1:325–327

    Article  CAS  Google Scholar 

  • de Araújo Junior RF, de Araújo AA, Pessoa JB, Freire Neto FPF, da Silva GR, Letairo Oliveira SC, de Carvalho TG, Silva HFO, Eugênio M, Sant’Anna C, Gasparotto LHS (2017) Anti-inflammatory, analgesic and anti-tumor properties of gold nanoparticles. Pharmacol Rep 69(1):119–129. https://doi.org/10.1016/j.pharep.2016.09.017

    Article  CAS  Google Scholar 

  • Devasagayam TPA, Boloor KK, Ramasarma T (2003) Method for estimating lipid peroxidation: an analysis of merits and demerits. Indian J Biochem Biophys 40(5):300–308

    CAS  PubMed  Google Scholar 

  • Di Guglielmo C, De Lapuente J, Porredon C, Ramos-López D, Sendra J, Borràs M (2012) In-vitro safety toxicology data for evaluation of gold nanoparticles-chronic cytotoxicity, genotoxicity and uptake. J Nanosci Nanotechnol 12(8):6185–6191

    Article  Google Scholar 

  • Dix TA, Aikens J (1993) Mechanisms and biological relevance of lipid peroxidation initiation. Chem Res Toxicol 6(1):2–18

    Article  CAS  Google Scholar 

  • Dreaden EC, Mackey MA, Huang X, Kang B, El-Sayed MA (2011) Beating cancer in multiple ways using nanogold. Chem Soc Rev 40(7):3391–3404. https://doi.org/10.1039/c0cs00180e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dreaden EC, Alkilany AM, Huang X, Murphy CJ, El-Sayed MA (2012) The golden age: gold nanoparticles for biomedicine. Chem Soc Rev 41(7):2740–2779. https://doi.org/10.1039/c1cs15237h

    Article  CAS  PubMed  Google Scholar 

  • Eustaquio T, Leary JF (2012) Single cell nanotoxicity assays of superparamagnetic iron oxide nanoparticles. Methods Mol Biol 926:69–85

    Article  CAS  Google Scholar 

  • Farmer EE, Davoine C (2007) Reactive electrophile species. Curr Opin Plant Biol 10(4):380–386. https://doi.org/10.1016/j.pbi.2007.04.019

    Article  CAS  PubMed  Google Scholar 

  • Faurschou M, Borregaard N (2003) Neutrophil granules and secretory vesicles in inflammation. Microbes Infect 5(14):1317–1327

    Article  CAS  Google Scholar 

  • Freese C, Uboldi C, Gibson MI, Unger RE, Weksler BB, Romero IA, Couraud PO, Kirkpatrick CJ (2012) Uptake and cytotoxicity of citrate-coated gold nanospheres: comparative studies on human endothelial and epithelial cells. Part Fibre Toxicol 9:23. https://doi.org/10.1186/1743-8977-9-23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu PP, Xia Q, Hwang H-M, Ray PC, Yu H (2014) Mechanism of nanotoxicity: generation of reactive oxygen species. J Food Drug Anal 22(1):64–75. https://doi.org/10.1016/j.jfda.2014.01.005

    Article  CAS  PubMed  Google Scholar 

  • Gornall AG, Bardawill CJ, David MM (1949) Determination of serum proteins by means of the biuret reaction. J Biol Chem 177(2):751–766

    Article  CAS  Google Scholar 

  • Hassan AM, Abdel-Aziem SH, El-Nekeety AA, Abdel-Wahhab MA (2015) Panax ginseng extract modulates oxidative stress, DNA fragmentation and up-regulate gene expression in rats subchronically treated with aflatoxin B1 and fumonisin B1. Cytotechnology 67(5):861–871

    Article  CAS  Google Scholar 

  • Jain S, Nair A, Shrivastava C (2015) Evaluation of oxidative stress marker malondialdehyde level in the cord blood of newborn infants. Int J Sci Study 3(6):73–76

    CAS  Google Scholar 

  • Kagan VE, Konduru NV, Feng W, Allen BL, Conroy J, Volkov Y, Vlasova II, Belikova NA, Yanamala N, Kapralov A, Tyurina YY, Shi J, Kisin ER, Murray AR, Franks J, Stolz D, Gou P, Klein-Seetharaman J, Fadeel B, Star A, Shvedova AA (2010) Carbon nanotubes degraded by neutrophilmyeloperoxidase induce less pulmonary inflammation. Nat Nanotechnol 5:354–359

    Article  CAS  Google Scholar 

  • Khlebstov N, Dykman L (2011) Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem Soc Rev 40(3):1647–1671. https://doi.org/10.1039/c0cs00018c Epub 2010

    Article  CAS  Google Scholar 

  • Lasagna-Reeves C, Gonzalez-Romero D, Barria MA, Olmedo I, Clos A, Sadagopa Ramanujam VM, Urayama A, Vergara L, Kogan MJ, Soto C (2010) Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. Biochem Biophys Res Commun 393:649–655

    Article  CAS  Google Scholar 

  • Lau D, Mollnau H, Eiserich JP, Freeman BA, Daiber A, Gehling UM, Brümmer J, Rudolph V, Münzel T, Heitzer T, Meinertz T, Baldus S (2005) Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Proc Natl Acad Sci U S A 102(2):431–436

    Article  CAS  Google Scholar 

  • Lee WM (2003) N. Drug-induced hepatotoxicity. Engl J Med 349(5):474–485

    Article  CAS  Google Scholar 

  • Morais T, Soares ME, Duarte JA, Soares L, Maia S, Gomes P, Pereira E, Fraga S, Carmo H, De Lourdes BM (2012) Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat. Eur J Pharm Biopharm 80:185–193

    Article  CAS  Google Scholar 

  • Nicol JR, Dixon D, Coulter JA (2015) Gold nanoparticle surface functionalization: a necessary requirement in the development of novel therapeutics. Nanomedicine (London) 10(8):1315–1326. https://doi.org/10.2217/nnm.14.219

    Article  CAS  Google Scholar 

  • Pan Y, Neuss S, Leifert A, Fischler M, Wen F, Simon U, Schmid G, Brandau W, Jahnen-Dechent W (2007) Size-dependent cytotoxicity of gold nanoparticles. Small 3(11):1941–1949. https://doi.org/10.1002/smll.200700378

    Article  CAS  PubMed  Google Scholar 

  • Panchapakesan B, Book-Newell B, Sethu P, Rao M, Irudayaraj J (2011) Gold nanoprobes for theranostics. Nanomedicine (London) 6:1787–1811

    Article  Google Scholar 

  • Perandones CE, Lllera AV, Peckham D, Stunzl LL, Ashman RF (1993) Regulation of apoptosis in-vitro in mature murine spleen T cell. J Immunol 151:3521–3529

    CAS  PubMed  Google Scholar 

  • Pissuwan D, Niidome T, Cortie MB (2011) The forthcoming applications of gold nanoparticles in drug and gene delivery systems. J Control Release 149(1):65–71. https://doi.org/10.1016/jconrel.2009.12.006

    Article  CAS  PubMed  Google Scholar 

  • Rieznichenko LS, Dybkova SM, Gruzina TG, Ulberg ZR, Todor IN, Lukyanova NY, Shpyleva SI, Chekhun VF (2012) Gold nanoparticles synthesis and biological activity estimation in- vitro and in-vivo. Exp Oncol 34(1):25–28

    CAS  PubMed  Google Scholar 

  • Rim K-T, Song S-W, Kim H-Y (2013) Oxidative DNA damage from nanoparticle exposure and its application to workers’ health: a literature review. Saf Health Work 4(4):177–186

    Article  Google Scholar 

  • Roberts RA, Ganey PE, Ju C, Kamendulis LM, Rusyn I, Klaunig JE (2007) Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis. Toxicol Sci 96(1):2–15

    Article  CAS  Google Scholar 

  • Singh N, Manshian B, Jenkins GJS, Griffiths SM, Williams PM, Maffeis TGG, Wright CHJ, Doak SH (2009) NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30(23-24):3891–3914. https://doi.org/10.1016/jbiomaterials.2009.04.009

    Article  CAS  PubMed  Google Scholar 

  • Smedsrod B, De Bleser PJ, Braet F, Lovisetti P, Vanderkerken K, Wisse E, Geerts A (1994) Cell biology of liver endothelial and Kupffer cells. Gut 35:1509–1516. https://doi.org/10.1136/gut.35.11.1509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thakor AS, Jokerst J, Zavaleta C, Massoud TF, Gambhir SS (2011) Gold nanoparticles: a revival in precious metal administration to patients. Nano Lett 11(10):4029–4036. https://doi.org/10.1021/nl202559p

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weber D, Davies MJ, Grune T (2015) Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: focus on sample preparation and derivatization conditions. Redox Biol 5:367–380. https://doi.org/10.1016/jredox.2015.06.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This study received no research grant; it was personally funded.

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Authors and Affiliations

  1. Department of Biochemistry, Landmark University, P.M.B, 1001, Omu-Aran, Nigeria

    O. J. Awakan, A. E. Ohue, O. S. Adeyemi, C. O. Nwonuma, T. D. Olaolu, O. O. Alejolowo & M. A. Ajibade

  2. Department of Physical Sciences, Landmark University, P.M.B, 1001, Omu-Aran, Nigeria

    A. O. Dada

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  1. O. J. Awakan
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Correspondence to O. J. Awakan.

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Awakan, O.J., Ohue, A.E., Adeyemi, O.S. et al. Orally administered gold nanoparticles caused mild oxidative stress in the lungs and liver of Wistar rats. Comp Clin Pathol 30, 483–491 (2021). https://doi.org/10.1007/s00580-021-03242-z

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