Effects of gold nanoparticles and oligonucleotide coated gold nanoparticles on oxidative stress parameters in rats

Year 2026, Volume: 30 Issue: 2, 614 - 628, 15.03.2026

Ahmet Aydın , Feyza Kelleci Çelik , Betül Sarı , Muhammed Hamitoğlu , Hande Sipahi , Mustafa Culha

https://doi.org/10.12991/jrespharm.1654495

https://izlik.org/JA54FX55MU

Abstract

Gold nanoparticles (AuNPs) are used in biomedical applications. Due to data gap for safety of them, this research aimed to evaluate both AuNPs and oligonucleotide coated AuNPs (O-AuNPs) at 100, 500, and 2500 µg/kg doses in rats. Oxidative stress parameters, cytokines, 3-Nitrotyrosine, and metallothionein levels were also measured. There were significant changes in catalase, superoxide dismutase and malondialdehyde in erythrocyte, liver, kidney and brain tissues of rats. Liver metallothionein decreased in the lowest dose AuNPs, lowest and mid-dose O-AuNPs. As a result, AuNPs seem to have some adverse effects on oxidative stress parameters. Further researches are needed to elucidate the safety of AuNPs and O-AuNPs.

Keywords

oligonucleotide coating , toxicity , inflammation , reactive oxygen species

Ethical Statement

None

Supporting Institution

None.

Project Number

None

Thanks

None.

References

• [1] Boisselier E, Astruc D. Gold nanoparticles in nanomedicine: Preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev. 2009; 38(6): 1759-1782. http://doi.org/10.1039/b806051g
• [2] Hall JB, Dobrovolskaia MA, Patri AK, McNeil SE. Characterization of nanoparticles for therapeutics. Nanomedicine. 2007; 2(6): 789-803. http://doi.org/10.2217/17435889.2.6.789
• [3] Caruthers SD, Wickline SA, Lanza GM. Nanotechnological applications in medicine. Curr Opin Biotechnol. 2007; 18(1): 26-30. http://doi.org/10.1016/j.copbio.2007.01.006
• [4] Samak MA, Elfakharany YM, Huessiny N, Alsemeh AE. Gold nanoparticles “AuNPs”-mediated amelioration of experimentally toxic-induced cerebellar syndrome: Insights into cytomolecular and immuno-histochemical modifications, with a focus on CREB/Tau modulation. Tissue and Cell. 2025; 93: 102725. https://doi.org/10.1016/j.tice.2025.102725
• [5] Kim T, Lee K, Gong MS, Joo SW. Control of gold nanoparticle aggregates by manipulation of interparticle interaction. Langmuir. 2005; 21(21): 9524-9528. http://doi.org/10.1021/la0504560
• [6] Daniel MC, Astruc D. Gold Nanoparticles: Assembly, Supramolecular Chemistry, Quantum-Size-Related Properties, and Applications Toward Biology, Catalysis, and Nanotechnology. Chem Rev. 2004; 104(1): 293-346. http://doi.org/10.1021/cr030698
• [7] Eustis S, El-Sayed MA. Why gold nanoparticles are more precious than pretty gold:Noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes. Chem Soc Rev. 2006; 35(3): 209-217. http://doi.org/10.1039/B514191E
• [8] Fröhlich E, Roblegg E. Models for oral uptake of nanoparticles in consumer products. Toxicology. 2012; 291(1-3): 10-17. http://doi.org/10.1016/j.tox.2011.11.004
• [9] Lu F, Doane TL, Zhu JJ, Burda C. Gold nanoparticles for diagnostic sensing and therapy. Inorg Chim Acta. 2012; 393: 142-153. http://doi.org/10.1016/j.ica.2012.05.038
• [10] Loscertales, E., López-Méndez, R., Mateo, J., Fraile, L. M., Udias, J. M., Espinosa, A., & España, S. Impact of gold nanoparticle size and coating on radiosensitization and generation of reactive oxygen species in cancer therapy. Nanoscale Adv. 2025; 7: 1204-1214. http://doi.org/10.1039/D4NA00773E
• [11] Tan YY, Yap PK, Xin Lim GL, Mehta M, Chan Y, Ng SW, Kapoor DN, Negi P, Anand K, Singh SK, Jha NK, Lim LC, Madheswaran T, Satija S, Gupta G, Dua K, Chellappan DK. Perspectives and advancements in the design of nanomaterials for targeted cancer theranostics. Chemico-Biological Interaction. 2020; 329: 1-15. http://doi.org/10.1016/j.cbi.2020.109221
• [12] Isoda K, Tanaka A, Fuzimori C, Echigoya M, Taira Y, Taira I, Shimizu Y, Akimoto Y, Kawakami H, Ishida I. Toxicity of Gold Nanoparticles in Mice due to Nanoparticle/Drug Interaction Induces Acute Kidney Damage. Nanoscale Research Letters. 2020; 15: 141. http://doi.org/10.1186/s11671-020-03371-4
• [13] Zhang XD, Wu HY, Wu D, Wang YY, Chang JH, Zhai ZB Meng AM, Liu PX, Zhang LA, Fan FY. Toxicologic effects of gold nanoparticles in vivo by different administration routes. Int J Nanomedicine. 2010; 5(1): 771-781. http://doi.org/10.2147/IJN.S8428
• [14] Alkilany AM, Murphy CJ. Toxicity and cellular uptake of gold nanoparticles: What we have learned so far? J Nanopart Res. 2010; 12(7): 2313-2333. http://doi.org/10.1007/s11051-010-9911-8
• [15] Falagan-Lotscha P, Grzincica EM, Murphya CJ. One low-dose exposure of gold nanoparticles induces long-term changes in human cells. PNAS. 2016; 113(47): 13318-13323. http://doi.org/10.1073/pnas.1616400113
• [16] Revia RA, Stephen ZR, Zhang M. Theranostic nanoparticles for RNA-based cancer treatment. Acc Chem Res. 2019; 52(6): 1496-1506. http://doi.org/10.1021/acs.accounts.9b00101
• [17] Limón-Pacheco J, Gonsebatt ME. The role of antioxidants and antioxidant-related enzymes in protective responses to environmentally induced oxidative stress. Mutat Res. 2009; 674(1-2): 137-147. http://doi.org/10.1016/j.mrgentox.2008.09.015
• [18] McCall MR, Frei B. Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic Biol Med. 1999; 26(7-8): 1034-1053. http://doi.org/10.1016/s0891-5849(98)00302-5
• [19] Mateo D, Morales P, A´valos A, Haza AI. Oxidative stress contributes to gold nanoparticle-induced cytotoxicity in human tumor cells. Toxicol Mech Method. 2014; 24: 161-172. http://doi.org/10.3109/15376516.2013.869783
• [20] de Oliveira CMB, Sakata RK, Issy AM, Gerola LR, Salomão R. Cytokines and pain. Rev Bras Anestesiol. 2011; 61: 2. http://doi.org/10.1016/S0034-7094(11)70029-0
• [21] Rincon M, Irvin CG. Role of IL-6 in Asthma and Other Inflammatory Pulmonary Diseases. Int J Biol Sci 2012; 8(9): 1281-1290. http://doi.org/10.7150/ijbs.4874
• [22] Kenny OM, McCarthy CM, Brunton NP, Hossain MB, Rai DK, Collins SG, Jones PW, Maguire AR, O'Brien NM. Anti-inflammatory properties of potato glycoalkaloids in stimulated Jurkat and Raw 264.7 mouse macrophages. Life Sci. 2013; 92(13): 775-82. http://doi.org/10.1016/j.lfs.2013.02.006
• [23] Cho WS, Cho M, Jeong J, Choi M, Cho HY, Han BS, Kim SH, Kim HO, Lim YT, Chung BH, Jeong J. Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles. Toxicol Appl Pharmacol. 2009; 236: 16-24. http://doi.org/10.1016/j.taap.2008.12.023
• [24] Shrivastava R, Kushwaha P, Bhutia YC, Flora S. Oxidative stress following exposure to silver and gold nanoparticles in mice. Toxicol Ind Health. 2016; 32: 1391-1404. http://doi.org/10.1177/0748233714562623
• [25] Fernandes KCM, Martins Jr. AC, de Oliveira AAS, Antunes LMG, de Syllos Cólus IM, Barbosa Jr. F, Barcelos GRM. Polymorphism of metallothionein 2A modifies lead body burden in workers chronically exposed to the metal. Public Health Genomics. 2016; 19: 47-52. http://doi.org/10.1159/000441713
• [26] Brundo MV, Pecoraro R, Marino F, Salvaggio A, Tibullo D, Saccone S, Bramanti V, Buccheri BA, Impellizzeri G, Scuderi V, Zimbone M, Privitera V. Toxicity evaluation of new engineered nanomaterials in Zebrafish. Frontiers in Physiology. 2016; 7: 130. http://doi.org/10.3389/fphys.2016.00130
• [27] Lee PC, Meisel D. Adsorption and surface-enhanced Raman of dyes on silver and gold sols. J Phys Chem. 1982; 86(17): 3391-3395. http://doi.org/10.1021/j100214a025
• [28] Leonavičienė L, Kirdaitė G, Bradūnaitė R, Vaitkienė D, Vasiliauskas A, Zabulytė D, Ramanavičienė A, Ramanavičius A, Ašmenavičius T, Mackiewicz Z. Effect of gold nanoparticles in the treatment of established collagen arthritis in rats. Medicina (Kaunas). 2012; 48(2): 91-101. http://doi.org/10.3390/medicina48020016
• [29] Kelleci Çelik F, Hamitoğlu M, Aydın A. Toxicological evaluation of the interaction between circadian rhythm activator; KL001 and general anesthetic; isoflurane. Biological Rhythm Research. 2019 https://doi.org/10.1080/09291016.2019.1698808
• [30] Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1): 265-275.
• [31] Bulucu F, Vural A, Aydin A, Sayal A. Oxidative stress status in adults with nephrotic syndrome. Clin Nephrol. 2000; 53(3): 169-173.
• [32] Aebi H. Catalase in vitro. Methods in Enzymol. 1984; 105(C): 121-126.
• [33] Lasagna-Reeves C, Gonzalez-Romero D, Barria MA, Olmedo I, Clos A, Ramanujam VMS, Urayama A, Vergara L, Kogan MJ, Soto C. Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. Biochem. Biophys. Res Commun. 2010; 393(4): 649-655. http://doi.org/10.1016/j.bbrc.2010.02.046
• [34] Chen YS, Hung YC, Liau I, Huang GS. Assessment of the in vivo toxicity of gold nanoparticles. Nanoscale Res. Lett 2009; 4(8): 858-864. http://doi.org/10.1007/s11671-009-9334-6
• [35] Sun PP, Lai CS, Hung CJ, Dhaiveegan P, Tsai ML, Chiu CL, Fang JM. Subchronic oral toxicity evaluation of gold nanoparticles in male and female mice. Heliyon. 2021; 7: 1204-1214.
• [36] Dhar S, Mali V, Bodhankar S, Shiras A, Prasad BLV, Pokharkar V. Biocompatible gellan gum-reduced gold nanoparticles: Cellular uptake and subacute oral toxicity studies. J Appl Toxicol. 2011; 31(5): 411-420. http://doi.org/10.1002/jat.1595
• [37] Torresan V, Forrer D, Guadagnini A, Badocco D, Pastore P, Selloni MCA, Coral D, Ceolin M, Fernández van Raap MB, Busato A, Marzola P, Spinelli AE, Amendola V. 4D Multimodal Nanomedicines Made of Non-Equilibrium Au-Fe Alloy Nanoparticles. ACS Nano. 2020; 14(10): 12840–12853. http://doi.org/10.1021/acsnano.0c03614
• [38] Kus-Liśkiewicz M, Fickers P, Ben Tahar I. Biocompatibility and Cytotoxicity of Gold Nanoparticles: Recent Advances in Methodologies and Regulations. Int J Mol Sci. 2021; 22(20): 10952. https://doi.org/10.3390/ijms222010952
• [39] Niżnik Ł, Noga M, Kobylarz D, Frydrych A, Krośniak A, Kapka-Skrzypczak L, Jurowski K. Gold Nanoparticles (AuNPs)-Toxicity, Safety and Green Synthesis: A Critical Review. Int J Mol Sci. 2024; 25(7): 4057. https://doi.org/10.3390/ijms25074057
• [40] Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004; 266(1-2): 37-56. http://doi.org/10.1023/b:mcbi.0000049134.69131.89
• [41] Siddiqi NJ, Abdelhalim MAK, El-Ansary AK, Alhomida AS, Ong WY. Identification of potential biomarkers of gold nanoparticle toxicity in rat brains. J Neuroinflammation. 2012; 9: 123.
• [42] Khan HA, Abdelhalim MAK, Al-Ayed MS, Alhomida AS. Effect of gold nanoparticles on glutathione and malondialdehyde levels in liver, lung and heart of rats. Saudi J Biol Sci. 2012; 19(4): 461-464. http://doi.org/10.1016/j.sjbs.2012.06.005
• [43] Saha SK, Roy P, Mondal MK, Roy D, Gayen P, Chowdhury P, Sinha Babu SP. Development of chitosan based gold nanomaterial as an efficient antifilarial agent: A mechanistic approach. Carbohydr Polym. 2017; 157: 1666-1676. http://doi.org/10.1016/j.carbpol.2016.11.047
• [44] Schulz M, Ma-Hock L, Brill S, Strauss V, Treumann S, Gröters S, van Ravenzwaay B, Landsiedel R. Investigation on the genotoxicity of different sizes of gold nanoparticles administered to the lungs of rats. Mutat Res. 2012; 745(1-2): 51-57. http://doi.org/10.1016/j.mrgentox.2011.11.016
• [45] Zheng D, Giljohann DA, Chen DL, Massicha MD, Wang XQ, Iordanov H, Mirkina CA, Paller AS. Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation. PNAS. 2012; 109(30): 11975-1198. http://doi.org/10.1073/pnas.1118425109
• [46] Witten, K. G., Bretschneider, J. C., Eckert, T., Richtering, W., & Simon, U. Assembly of DNA-functionalized gold nanoparticles studied by UV/Vis-spectroscopy and dynamic light scattering. Phys Chem Chem Phys. 2008; 10(14): 1870-1875. https://doi.org/10.1039/B719762D
• [47] Zhang XD, Wu HY, Wu D, Wang YY, Chang JH, Zhai ZB, Meng AM, Liu PX, Zhang LA, Fan FY. Toxicologic effects of gold nanoparticles in vivo by different administration routes. Int J Nanomedicine. 2010; 5 771–781. http:// doi.org/10.2147/IJN.S8428