Abstract
Currently most of the applications of silver nanoparticles are in antibacterial/antifungal agents in medicine and biotechnology, textile engineering, water treatment and silver-based consumer products. However, the effects of silver nanoparticles on human body, especially on the central nervous system, are still unclear. To study the mechanisms underlying the effects of silverpoly(amidehydroxyurethane) coated silver nanoparticles on brain functions, we subjected male Wistar rats to chronic treatments with silver-29 nm (5 µg/kg and 10 µg/kg) and silver-23 nm (5 µg/kg and 10 µg/kg) nanoparticles for 7 days. We evaluated the effects of nanoparticles size and structure on rat memory function. Memory processes were studied by means of two cognitive tasks (Y-maze and radial arm-maze). Exposure to silver nanoparticles significantly decreased spontaneous alternation in the Y-maze task and working memory functions in the radial arm-maze task, suggesting that nanoparticles have effects on short-term memory. We found no effects on long-term memory, which we assessed by reference memory trials in the radial arm-maze task. We found that memory deficits were significantly correlated with oxidative stress generation only in the Y-maze task. Our findings suggest that silver nanoparticles may induce an impairment of memory functions by increasing oxidative stress in the brain. The use of silver nanoparticles for medical purposes therefore requires careful consideration, particularlyif it involves exposure of the human brain.
Similar content being viewed by others
References
Toshima N., Nanoscale Materials, In: M. Liz-Marzan L., Kamat P.V., (Eds.), Kluwer Academic Pub., London, 2003, 79–96
Nam J.M., Thaxton C.S., Mirkin C.A., Nanoparticlebased bio-bar codes for the ultrasensitive detection of proteins, Science, 2003, 301, 1884–1886
Tkachenko A.G., Xie H., Coleman D., Glomm W., Ryan J., Anderson M.F., et al., Multifunctional gold nanoparticle peptide complexes for nuclear targeting, J. Am. Chem. Soc., 2003, 125, 4700–4701
Hirsch L.R., Stafford R.J., Bankson J.A., Sershen S.R., Rivera B., Price R.E., et al., Nanoshellmediated near-infrared thermal therapy of tumors under magnetic resonance guidance, Proc. Natl. Acad. Sci. USA, 2003, 100, 13549–13554
Burda C., Chen X., Narayanan R., El-Sayed M.A., Chemistry and properties of nanocrystals of different shapes, Chem. Rev., 2005, 105, 1025–1102
Gupta A., Silver S., Silver as biocide:Will resistance become a problem?, Nat. Biotechnol., 1998, 16, 888
Ji J.H., Jung J.H., Kim S.S., Yoon J.U., Park J.D., Choi B.S., et al., Twenty-eight-day inhalation toxicity study of silver nanoparticles in Sprague-Dawley rats, Inhal. Toxicol., 2007, 19, 857–871
Lockman P.R., Koziara J.M., Mumper R.J., Allen D.D., Nanoparticle surface charges alter blood-brain barrier integrity and permeability, J. Drug. Target., 2004, 12, 635–641
Kreyling W.G., Semmler M., Erbe F., Mayer P., Takenaka S., Schulz H., et al., Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low, J. Toxicol. Environ. Health Part A, 2002, 65, 1513–1530
Oberdorster G., Sharp Z., Atudorei V., Elder A., Gelein R., Kreyling W., et al., Translocation of inhaled ultrafine particles to the brain, Inhal. Toxicol., 2004, 16, 437–445
Ma L., Liu J., Li N., Wang J., Duan Y., Yan J., et al., Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO2 delivered to the abdominal cavity, Biomaterials, 2010, 31, 99–105
Hu R., Gong X., Duan Y., Li N., Che Y., Cui Y., et al., Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles, Biomaterials, 2010, 31, 8043–8050
Sharma H.S., Nanoneuroscience: emerging concepts on nanoneurotoxicity and nanoneuroprotection, Nanomedicine, 2007, 2, 753–758
Sharma H.S., Sharma A., Nanoparticles aggravate heat stress induced cognitive deficits, blood-brain barrier disruption, edema formation and brain pathology, Prog. Brain Res., 2007, 162, 245–273
Kim Y.S., Kim J.S., Cho H.S., Rha D.S., Kim J.M., Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats, Inhal. Toxicol., 2008, 20, 575–583
Liu Z., Ren G., Zhang T., Yang Z., Action potential changes associated with the inhibitory effects on voltage-gated sodium current of hippocampal CA1 neurons by silver nanoparticles, Toxicology, 2009, 264, 179–184
Cha K., Hong H.W., Choi Y.G., Lee M.J., Park J.H., Chae H.K., et al., Comparison of acute responses of mice livers to short-term exposure to nano-sized or micro-sized silver particles, Biotechnol. Lett., 2008, 30, 1893–1899
Shin S.H., Ye M.K., Kim H.S., Kang H.S., The effects of nano-silver on the proliferation and cytokine expression by peripheral blood mononuclear cells, Int. Immunopharmacol., 2007, 7, 1813–1818
Tang M., Xing T., Zeng J., Wang H., Li C., Yin S., et al., Unmodified CdSe quantum dots induce elevation of cytoplasmic calcium levels and impairment of functional properties of sodium channels in rat primary cultured hippocampal neurons, Environ. Health Perspect., 2008, 116, 915–922
Hussain S.M., Javorina A.K., Schrand A.M., Duhart H.M., Ali S.F., Schlager J.J., The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion, Toxicol. Sci., 2006, 92, 456–463
Cui K., Luo X., Xu K., Ven Murthy M.R., Role of oxidative stress in neurodegeneration: recent developments in assay methods for oxidative stress and nutraceutical antioxidants, Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 2004, 28, 771–799
Curtin J.F., Donovan M., Cotter T.G., Regulation and measurement of oxidative stress in apoptosis, J. Immunol. Methods, 2002, 265, 49–72
Arora S., Jain J., Rajwade J.M., Paknikar K.M., Cellular responses induced by silver nanoparticles: In vitro studies, Toxicol. Lett., 2008, 179, 93–100
Rahman M.F., Wang J., Patterson T.A., Saini U.T., Robinson B.L., Newport G.D., et al., Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticles, Toxicol. Lett., 2009, 187, 15–21
Ahamed M., Posgai R., Gorey T.J., Nielsen M., Hussain S.M., Rowe J.J., Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster, Toxicol. Appl. Pharmacol., 2010, 242, 263–269
Choi J.E., Kim S., Ahn J.H., Youn P., Kang J.S., Park K., et al., Induction of oxidative stress and apoptosis by silver nanoparticles in the liver of adult zebrafish, Aquat. Toxicol., 2010, 100, 151–159
Sun L., Singh A.K., Vig K., Pillai S.R., Singh S.R., Silver nanoparticles inhibit replication of respiratory syncytial virus, J. Biomed. Biotechnol., 2008, 4, 149–158
Duran N., Marcato P.D., De Conti R., Alves O.L., Costa F.T.M., Brocchi M., Potential use of silver nanoparticles on pathogenic bacteria, their toxicity and possible mechanisms of action, J. Braz. Chem. Soc., 2010, 21, 949–959
Karelson E., Bogdanovic N., Garlind A., Winblad B., Zilmer K., Kullisaar T., et al., The cerebrocortical areas in normal brain aging and in Alzheimer’s disease: noticeable differences in the lipid peroxidation level and in antioxidant defense, Neurochem. Res., 2001, 26, 353–361
Tang S., Tang Y., Gao F., Liu Z., Meng X., Ultrasonic electrodeposition of silver nanoparticles on dielectric silica spheres, Nanotechnology, 2007, 18, 1–6
Melnig V., Ciobanu C., Characterization of water-soluble polyamidhydroxyurethane for biological applications, J. Optoelectron. Adv. M., 2005, 7, 2809–2815
Apostu M.O., Melnig V., Tunable temperature behaviour of water-soluble polyamidhydroxyurethane, J. Optoelectron. Adv. M., 2006, 8, 1044–1047
Melnig V., Pohoata V., Obreja L., Garlea A., Cazacu M., Water-soluble polyamidhydroxyuretane swelling behaviour, J. Optoelectron. Adv. M., 2006, 8, 1040–1043
Riddick T.M., Control of colloid stability through zeta potential, Livingston Pub. Co., New York, 1968
Hritcu L., Nabeshima T., Kainic acid lesion-induced spatial memory deficits of rats, Cent. Eur. J. Biol., 2009, 4, 179–185
Hritcu L., Clicinschi M., Nabeshima T., Brain serotonin depletion impairs short-term memory, but not long-term memory in rats, Physiol. Behav., 2007, 91, 652–657
Winterbourne C.C., How Kins R.E., Brain M., Carrell R.W., The estimation of red cell superoxide dismutase activity, J. Lab. Clin. Med., 1975, 85, 327–341
Sharma M., Gupta Y.K., Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats, Life Sci., 2002, 71, 2489–2498
Ohkawa H., Ohishi N., Yagi K., Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction, Anal. Biochem., 1979, 95, 351–358
Tamba B.I., Jaba I.M., Bohotin C.R., Neagu A.N., Mungiu O.C., Wirth A., et al., Preliminary experimental data regarding the bioavailability and biodistribution of systematically administred TAW20 silica nanoparticle, In: 2nd European Conference for Clinical Nanomedicine-Nanotechnology for novel solutions in medicine, European Foundation for clinical nanomedicine (27–29 Apr 2009, Basel, Switzerland), 2009, III-80
Downs R.T., Bartelmehs K.L., Gibbs G.V., Boysen Jr. M.B., Interactive software for calculating and displaying X-ray or neutron powder diffractometer patterns of crystalline materials, Am. Mineral., 1993, 78, 1104–1107
Liau S.Y., Read D.C., Pugh W.J., Furr J.R., Russell A.D., Interaction of silver nitrate with readily identifiable groups: Relationship to the antibacterial action of silver ions, Lett. Appl. Microbiol., 1997, 25, 279–283
Sondi I., Salopek-Sondi B., Silver nanoparticles as antimicrobial agent: A case study on E. coli as a model for Gram-negative bacteria, J. Colloid Interface Sci., 2004, 275, 177–182
Brown D.M., Wilson M.R., MacNee W., Stone V., Donaldson K., Size-dependent proinflammatory effects of ultrafine polystyrene particles: A role for surface area and oxidative stress in the enhanced activity of ultrafines, Toxicol. Appl. Pharmacol., 2001, 175, 191–199
Muller M., Mackeben S., Muller-Goymann C.C., Physicochemical characterisation of liposomes with encapsulated local anaesthetics, Int. J. Pharm., 2004, 274, 139–148
Foley S., Crowley C., Smaihi M., Bonfils C., Erlanger B.F., Seta P., et al., Cellular localisation of a water-soluble fullerene derivative, Biochem. Biophys. Res. Commun., 2002, 294, 116–119
Block M.L., Wu X., Pei Z., Li G., Wang T., Qin L., et al., Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase, FASEB J., 2004, 18, 1618–1620
Peters A., Veronesi B., Calderon-Garciduenas L., Gehr P., Chen L.C., Geiser M., et al., Translocation and potential neurological effects of fine and ultrafine particles a critical update, Part Fibre Toxicol., 2006, 3, 1–13
Carlson C., Hussain S.M., Schrand A.M., Braydich-Stolle L.K., Hess K.L., Jones R.L., et al., Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species, J. Phys. Chem. B, 2008, 112, 13608–13619
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Hritcu, L., Stefan, M., Ursu, L. et al. Exposure to silver nanoparticles induces oxidative stress and memory deficits in laboratory rats. cent.eur.j.biol. 6, 497–509 (2011). https://doi.org/10.2478/s11535-011-0022-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2478/s11535-011-0022-z