Abstract
Silver nanoparticles (AgNP) are known to penetrate the brain and cause pathological changes in central nervous system (CNS) functions. Still, it remains unclear whether AgNP solutions as antimicrobial agents are safe for humans. The attempt was undertaken to assess the risk of commercial silver nanoparticles for CNS, using a rat as a model and creating conditions as close as possible to human intake of aqueous AgNP solutions. The silver nanoparticle solutions prepared with natural stabilizer were used, a low dosage (51 μg/kg), intake with drinking water, and long-time exposure. We determined the effect of the AgNP solution on some indices of animal behavior—motor activity, anxiety, and short-term habituation (non-associative learning)—1 and 2 months after the start of the consumption and three months after the AgNP withdrawal. After the 2-month course, rats showed (1) an increase in motor activity and a decrease in anxiety-phobic levels under a stressful environment of a classic open field test, (2) a lack of short-term habituation in the acoustic startle, and (3) presence of the nanoparticles in the hippocampus, frontal cortex, and striatum as detected by transmission electron microscopy. These signs disappeared three months after the AgNP withdrawal. The results suggest that under experimental conditions close to actual human consumption, silver nanoparticles do not have a long-term adverse effect on the CNS functions.
Similar content being viewed by others
REFERENCES
A. B. G. Lansdown, Crit. Rev. Toxicol. 37, 237 (2007). https://doi.org/10.1080/10408440601177665
G. Oberdorster, J. Int. Med. 267, 89 (2010). https://doi.org/10.1111/j.1365-2796.2009.02187.x
H. J. Johnston, G. Hutchison, and F. M. Christensen, Crit. Rev. Toxicol. 40, 328 (2010). https://doi.org/10.3109/10408440903453074
S. Arora, J. M. Radjwade, and K. M. Paknikar, Toxicol. Appl. Pharmacol. 258, 151 (2012). https://doi.org/10.1016/j.taap.2011.11.010
Z. Lan and W.-X. Yang, Nanomedicine 7, 579 (2012). https://doi.org/10.2217/nnm.12.20
A. Pietroiusti, Nanoscale 4, 1231 (2012). https://doi.org/10.1039/C2NR11688J
J. Pulit-Prociak, K. Stokłosa, and M. Banach, Environ. Chem. Lett. 15, 59 (2014). https://doi.org/10.1007/s10311-014-0490-2
V. Kumar, N. Sharma, and S. S. Maitra, Int. Nano Lett. 7, 243 (2017). https://doi.org/10.1007/s40089-017-0221-3
P. A. Schulte, V. Leso, M. Niang, and I. Iavicoli, Scand. J. Work. Environ. Health 45, 217 (2019). https://doi.org/10.5271/sjweh.3800
M. Rai, A. Yadav, and A. Gade, Biotechnol. Adv. 27, 76 (2009). https://doi.org/10.1016/j.biotechadv.2008.09.002
D. R. Monteiro, L. F. Gorup, A. S. Takamiya, et al., Int. J. Antimicrob. Agents 34, 103 (2009). https://doi.org/10.1016/j.ijantimicag.2009.01.017
H. H. Lara, E. N. Garza-Treviño, L. Ixtepan-Turrent, et al., J. Nanobiotechnol. 9, 30 (2011). https://doi.org/10.1186/1477-3155-9-30
G. E. Krichevsky, Application of Metal Nanoparticles in Medicine, Nanotechnological Society of Russia. http://www.rusnor.org/pubs/articles/15479.htm.
M. Korani, E. Ghazizadeh, S. Korani, et al., Eur. J. Nanomed. 7, 51 (2015). https://doi.org/10.1515/ejnm-2014-0032
Y. S. Kim, M. Y. Song, J. D. Park, et al., Part. Fibre Toxicol. 7, 20 (2010). https://doi.org/10.1186/1743-8977-7-20
E.-J. Park, E. Bae, J. Yi, et al., Environ. Toxicol. Pharmacol. 30, 162 (2010). https://doi.org/10.1016/j.etap.2010.05.004
I. V. Gmoshinski, A. A. Shumakova, V. A. Shipelin, G. Y. Maltsev, and S. A. Khotimchenko, Nanotechnol. Russ. 11, 646 (2016). https://doi.org/10.1134/S1995078016050074
A. Pietroiusti, L. Campagnolo, and B. Fadeel, Small 9, 1557 (2012). https://doi.org/10.1002/smll.201201463
M. Ema, H. Okuda, M. Gamo, et al., Reprod. Toxicol. 67, 149 (2017). https://doi.org/10.1016/j.reprotox.2017.01.005
A. A. Antsiferova, Y. P. Buzulukov, V. A. Demin, V. F. Demin, P. K. Kashkarov, D. A. Rogatkin, E. N. Petritskaya, and L. F. Abaeva, Nanotechnol. Russ. 10, 100 (2015). https://doi.org/10.1134/S1995078015010024
A. A. Antsiferova, Y. P. Buzulukov, P. K. Kashkarov, and M. V. Kovalchuk, Crystallogr. Rep. 61, 1020 (2016). https://doi.org/10.7868/S0023476116060035
K. Dziendzikowska, J. Gromadzka-Ostrowska, A. Lankoff, et al., J. Appl. Toxicol. 32, 920 (2012). https://doi.org/10.1002/jat.2758
H. S. Sharma, Nanomedicine 2, 753 (2007). https://doi.org/10.2217/17435889.2.6.753
J. Tang, L. Xiong, G. Zhou, et al., J. Nanosci. Nanotechnol. 10, 6313 (2010). https://doi.org/10.1166/jnn.2010.2625
A. Sharma, D. F. Muresanu, R. Patnaik, et al., Mol. Neurobiol. 48, 386 (2013). https://doi.org/10.1007/s12035-013-8500-0
W. J. Trickler, S. M. Lantz, R. C. Murdock, et al., Toxicol. Sci. 118, 160 (2010). https://doi.org/10.1093/toxsci/kfq244
A. M. Khan, B. Korzeniowska, V. Gorshkov, et al., Nanotoxicology 13, 221 (2019). https://doi.org/10.1080/17435390.2018.1540728
M. Safari, S. A. Bidgoli, and S. M. Rezayat, Nanomed. J. 3 (2), 83 (2016). https://doi.org/10.7508/nmj.2016.02.002
B. Zhang, N. Na Liua, Q. S. Liua, et al., Ecotoxicol. Environ. Saf. 198, 110674 (2020). https://doi.org/10.1016/j.ecoenv.2020.110674
L. Hritcu, M. Stefan, L. Ursu, et al., Cent. Eur. J. Biol. 6, 497 (2011). https://doi.org/10.2478/s11535-011-0022-z
Y. Liu, W. Guan, G. Ren, et al., Toxicol. Lett. 209, 227 (2012). https://doi.org/10.1016/j.toxlet.2012.01.001
P. Liu, Z. Huang, and N. Gu, Ecotoxicol. Environ. Saf. 87, 124 (2013). https://doi.org/10.1016/j.ecoenv.2012.10.014
Y. Zhang, S. A. Ferguson, F. Watanabe, et al., Small 9, 1715 (2013). https://doi.org/10.1002/smll.201201548
N. Yin, Y. Zhang, Z. Yun, et al., Toxicol. Lett. 237, 112 (2015). https://doi.org/10.1016/j.toxlet.2015.06.007
O. A. Zeinalov, S. P. Kombarova, D. V. Bagrov, et al., Obzory Klin. Farmakol. Lekarst. Terap. 14 (4), 42 (2016). https://doi.org/10.17816/RCF14442-51
B. Dąabrowska-Bouta, M. Zięba, J. Orzelska-Górka, et al., Toxicology 363–364, 29 (2016). https://doi.org/10.1016/j.tox.2016.07.007
A. Antsiferova, M. Kopaeva, and P. Kashkarov, Materials 11, 558 (2018). https://doi.org/10.3390/ma11040558
A. Antsiferova, M. Kopaeva, V. N. Kochkin, et al., Toxics 9, 30 (2021). https://doi.org/10.3390/toxics9020030
A. N. Ivlieva, E. N. Petritskaya, D. A. Rogatkin, et al., Phys. Part. Nucl. Lett. 18, 250 (2021).
E. M. Egorova and A. A. Kubatiev, Nanotechnology: Research Methodology for the Effect of Metal Nanoparticles on Biological Objects (Yurait, Moscow, 2020) [in Russian].
Vitargol, Elusan LLC. https://vitargol.ru/nanosilver. Accessed May 26, 2021.
E. M. Egorova, A. A. Kubatiev, and V. I. Shvets, Biological Effects of Metal Nanoparticles (Moscow, Nauka, 2014), p. 172 (in Russian).
E. M. Egorova and L. S. Sosenkova, “A method of obtaining aqueous solutions of silver nanoparticles with a natural reducing agent,” Patent RF No. 2618270 (2016).
S. A. Kedik, A. V. Panov, V. S. Tyukova, and M. S. Zolotareva, Razrab. Pegistr. Lekarst. Sredstv 16 (3), 68 (2016).
P. dos Passos Menezesa, T. de Araujo Andradea, L. A. Frank, et al., Int. J. Pharm. 559, 312 (2019). https://doi.org/10.1016/j.ijpharm.2019.01.041
Colloidal Silver Forte, Nature Sunshine Products, Inc. https://natr.ru/catalog/bad/kolloidnoe-serebro-forte/?sphrase_id=21898.
T. A. Gus’kova, Toksikol. Vestn., No. 5, 2 (2010).
V. I. Rodina, N. A. Krupina, G. N. Kryzhanovskii, and N. B. Oknina, Zh. Vyssh. Nerv. Deyat. 43, 1006 (1993).
A. A. Walf and Ch. A. Frye, Nat. Protoc. 2, 322 (2007). https://doi.org/10.1038/nprot.2007.44
N. A. Krupina, N. N. Khlebnikova, and I. N. Orlova, Patol. Fiziol. Eksp. Ter. 59 (4), 4 (2015).
B. Valsamis and S. Schmid, J. Vis. Exp., No. 55, e3446 (2011). https://doi.org/10.3791/3446
J. P. Wilcoxon, R. L. Williamson, and R. Baughman, J. Chem. Phys. 98, 9933 (1993). https://doi.org/10.1063/1.464320
R. Kovner, J. A. Oler, and N. H. Kalin, Am. J. Psych. 176, 987 (2019). https://doi.org/10.1176/appi.ajp.2019.19101064
T. M. Florio, E. Scarnati, I. Rosa, et al., CNS Neurosci. Ther. 24, 677 (2018). https://doi.org/10.1111/cns.12987
J. Skalska and L. Struzyńska, Folia Neuropathol. 53, 281 (2015).
Y. P. Buzulukov, I. V. Gmoshinski, A. A. Ansiferova, et al., Nano Hybrids Compos. 13, 199 (2017).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The authors declare that they have no conflicts of interest.
Rights and permissions
About this article
Cite this article
Egorova, E.M., Krupina, N.A., Kaba, S.I. et al. The Effect of Aqueous Solution of Silver Nanoparticles on Rat Behavior. Nanotechnol Russia 17, 248–260 (2022). https://doi.org/10.1134/S2635167622020082
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S2635167622020082