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Environmental Science and Pollution Research

, Volume 25, Issue 17, pp 16922–16932 | Cite as

Intranasal instillation of iron oxide nanoparticles induces inflammation and perturbation of trace elements and neurotransmitters, but not behavioral impairment in rats

  • Dalel Askri
  • Souhir Ouni
  • Said Galai
  • Josiane Arnaud
  • Benoit Chovelon
  • Sylvia G. Lehmann
  • Nathalie Sturm
  • Mohsen Sakly
  • Michel Sève
  • Salem Amara
Research Article

Abstract

Over the last decades, engineered nanomaterials have been widely used in various applications due to their interesting properties. Among them, iron oxide nanoparticles (IONPs) are used as theranostic agents for cancer, and also as contrast agents in magnetic resonance imaging. With the increasing production and use of these IONPs, there is an evident raise of IONP exposure and subsequently a higher risk of adverse outcome for humans and the environment. In this work, we aimed to investigate the effects of sub-acute IONP exposure on Wistar rat, particularly (i) on the emotional and learning/memory behavior, (ii) on the hematological and biochemical parameters, (iii) on the neurotransmitter content, and (vi) on the trace element homeostasis. Rats were treated during seven consecutive days by intranasal instillations at a dose of 10 mg/kg body weight. The mean body weight increased significantly in IONP-exposed rats. Moreover, several hematological parameters were normal in treated rats except the platelet count which was increased. The biochemical study revealed that phosphatase alkaline level decreased in IONP-exposed rats, but no changes were observed for the other hepatic enzymes (ALT and AST) levels. The trace element homeostasis was slightly modulated by IONP exposure. Sub-acute intranasal exposure to IONPs increased dopamine and norepinephrine levels in rat brain; however, it did not affect the emotional behavior, the anxiety index, and the learning/memory capacities of rats.

Keywords

Iron oxide nanoparticles Rat Inflammation Behavior Trace elements Neurotransmitters 

Notes

Acknowledgements

We would like to thank Prof. Lassaad El Mir for providing iron oxide nanoparticles and the equipex NanoID (ANR-10-EQPX-39) for the access to the nanoZS. Thanks also to the Tunisian Ministry of Higher Education and Scientific Research and the Auvergne Rhone Alpes Region (grant no. 16.007278.01 for Dalel Askri) for their funding.

Compliance with ethical standards

The experimental protocols were approved by the Medical Ethical Committee for the Care and Use of Laboratory Animals of Pasteur Institute of Tunis (approval number: LNFP/Pro 152012).

Conflict of interest

The authors report no conflicts of interest in this work.

References

  1. Ai J, Biazar E, Jafarpour M, Montazeri M, Majdi A, Aminifard S, Zafari M, Akbari HR, Rad HG (2011) Nanotoxicology and nanoparticle safety in biomedical designs. Int J Nanomedicine 6:1117–1127Google Scholar
  2. Amara S, Ben-Slama I, Mrad I, Rihane N, Jeljeli M, el-Mir L, Ben-Rhouma K, Rachidi W, Sève M, Abdelmelek H, Sakly M (2014) Acute exposure to zinc oxide nanoparticles does not affect the cognitive capacity and neurotransmitters levels in adult rats. Nanotoxicology 8(sup1):208–215. Available at.  https://doi.org/10.3109/17435390.2013.879342 CrossRefGoogle Scholar
  3. Announcement, S., 2015. FDA strengthens warnings and changes prescribing instructions to decrease the risk of serious allergic reactions with anemia drug Feraheme (ferumoxytol )., pp.1–4Google Scholar
  4. Bleeker EAJ, de Jong WH, Geertsma RE, Groenewold M, Heugens EHW, Koers-Jacquemijns M, van de Meent D, Popma JR, Rietveld AG, Wijnhoven SWP, Cassee FR, Oomen AG (2013) Considerations on the EU definition of a nanomaterial: science to support policy making. Regul Toxicol Pharmacol 65(1):119–125CrossRefGoogle Scholar
  5. Chua AC, Morgan EH (1996) Effects of iron deficiency and iron overload on manganese uptake and deposition in the brain and other organs of the rat. Biol Trace Elem Res 55(1–2):39–54 Available at: http://www.ncbi.nlm.nih.gov/pubmed/8971353 CrossRefGoogle Scholar
  6. Cortajarena, A.L. et al., 2014. Engineering iron oxide nanoparticles for clinical settings. Nanobiomedicine, 1(2), p.doi:  https://doi.org/10.5772/58841. Available at: http://www.intechopen.com/journals/nanobiomedicine/engineering-iron-oxide-nanoparticles-for-clinical-settings
  7. Deguil J, Chavant F, Lafay-Chebassier C, Pérault-Pochat MC, Fauconneau B, Pain S (2010) Neuroprotective effect of PACAP on translational control alteration and cognitive decline in MPTP Parkinsonian mice. Neurotox Res 17(2):142–155CrossRefGoogle Scholar
  8. Elias, A. & Tsourkas, A., 2009. Imaging circulating cells and lymphoid tissues with iron oxide nanoparticles. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program, pp.720–726Google Scholar
  9. Enkel T et al (2014) Reduced expression of nogo-a leads to motivational deficits in rats. Front Behav Neurosci 8(January):1–7 Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3898325&tool=pmcentrez&rendertype=abstract Google Scholar
  10. Grover VA, Hu J, Engates KE, Shipley HJ (2012) Adsorption and desorption of bivalent metals to hematite nanoparticles. Environ Toxicol Chem 31(1):86–92CrossRefGoogle Scholar
  11. Hasan DM, Amans M, Tihan T, Hess C, Guo Y, Cha S, Su H, Martin AJ, Lawton MT, Neuwelt EA, Saloner DA, Young WL (2012) Ferumoxytol-enhanced MRI to image inflammation within human brain arteriovenous malformations: a pilot investigation. Transl Stroke Res 3(SUPPL. 1):166–173CrossRefGoogle Scholar
  12. Huang HS, Hainfeld JF (2013) Intravenous magnetic nanoparticle cancer hyperthermia. Int J Nanomedicine 8:2521–2532Google Scholar
  13. Von Hundelshausen P, Weber C (2007) Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res 100(1):27–40CrossRefGoogle Scholar
  14. Imam SZ, Lantz-McPeak SM, Cuevas E, Rosas-Hernandez H, Liachenko S, Zhang Y, Sarkar S, Ramu J, Robinson BL, Jones Y, Gough B, Paule MG, Ali SF, Binienda ZK (2015) Iron oxide nanoparticles induce dopaminergic damage: in vitro pathways and in vivo imaging reveals mechanism of neuronal damage. Mol Neurobiol 52(2):913–926CrossRefGoogle Scholar
  15. Kim E, Kim JM, Kim L, Choi SJ, Park IS, Han JY, Chu YC, Choi ES, Na K, Hong SS (2016) The effect of neutral-surface iron oxide nanoparticles on cellular uptake and signaling pathways. Int J Nanomedicine 11:4595–4607.  https://doi.org/10.2147/IJN.S110332 
  16. Kim Y, Kong SD, Chen LH, Pisanic TR II, Jin S, Shubayev VI (2013) In vivo nanoneurotoxicity screening using oxidative stress and neuroinflammation paradigms. Nanomedicine 9(7):1057–1066CrossRefGoogle Scholar
  17. Labrie V et al (2009) Genetic inactivation of D-amino acid oxidase enhances extinction and reversal learning in mice. Learn Memory (Cold Spring Harbor, NY) 16(1):28–37.  https://doi.org/10.1101/lm.1112209
  18. Lemine OM, Omri K, Iglesias M, Velasco V, Crespo P, de la Presa P, el Mir L, Bouzid H, Yousif A, al-Hajry A (2014) ??-Fe2O3by sol-gel with large nanoparticles size for magnetic hyperthermia application. J Alloys Compd 607:125–131. Available at.  https://doi.org/10.1016/j.jallcom.2014.04.002 CrossRefGoogle Scholar
  19. Lu M, Cohen MH, Rieves D, Pazdur R (2010) FDA report: ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease. Am J Hematol 85(5):315–319Google Scholar
  20. Maaroufi K, Ammari M, Jeljeli M, Roy V, Sakly M, Abdelmelek H (2009) Impairment of emotional behavior and spatial learning in adult Wistar rats by ferrous sulfate. Physiol Behav 96(2):343–349CrossRefGoogle Scholar
  21. Maher BA, Ahmed IAM, Karloukovski V, MacLaren DA, Foulds PG, Allsop D, Mann DMA, Torres-Jardón R, Calderon-Garciduenas L (2016) Magnetite pollution nanoparticles in the human brain. Proc Natl Acad Sci 113(39):10797–10801. Available at.  https://doi.org/10.1073/pnas.1605941113 CrossRefGoogle Scholar
  22. Morris R (1984) Developments of a water maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:7336–7336CrossRefGoogle Scholar
  23. Nieoullon A (2002) Dopamine and the regulation of cognition and attention. Prog Neurobiol 67(1):53–83CrossRefGoogle Scholar
  24. Park E-J, Kim H, Kim Y, Yi J, Choi K, Park K (2010) Inflammatory responses may be induced by a single intratracheal instillation of iron nanoparticles in mice. Toxicology 275(1–3):65–71 Available at: http://linkinghub.elsevier.com/retrieve/pii/S0300483X10002465 CrossRefGoogle Scholar
  25. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14(3):149–167CrossRefGoogle Scholar
  26. Pitkethly M (2008) Nanotechnology: past, present, and future. Nano Today 3(3–4):6Google Scholar
  27. Remy P, Doder M, Lees A, Turjanski N, Brooks D (2005) Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128(6):1314–1322CrossRefGoogle Scholar
  28. Van Rooy I et al (2011) In vivo methods to study uptake of nanoparticles into the brain. Pharm Res 28(3):456–471CrossRefGoogle Scholar
  29. Sadeghi L, Yousefi Babadi V, Espanani HR (2015) Toxic effects of the Fe2O3 nanoparticles on the liver and lung tissue. Bratislavske lekarske listy 116(6):373–378Google Scholar
  30. Sheida E et al (2017) The effect of iron nanoparticles on performance of cognitive tasks in rats. Environ Sci Poll Res 24(9):8700–8710 Available at: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85013081018&doi=10.1007%2Fs11356-017-8531 6&partnerID=40&md5=626b2c261f10e38bc9b09e725b40e087CrossRefGoogle Scholar
  31. Shirband A et al (2014) Dose-dependent effects of iron oxide nanoparticles on thyroid hormone concentrations in liver enzymes: possible tissue destruction. Global J Med Res Studies 1(1):28–31Google Scholar
  32. Simko M, Mattsson M-O (2014) Interactions between nanosized materials and the brain. Curr Med Chem 21(37):4200–4214 Available at: http://www.eurekaselect.com/openurl/content.php?genre=article&issn=0929-8673&volume=21&issue=37&spage=4200 CrossRefGoogle Scholar
  33. Sun Z et al (2014) Magnetic field enhanced convective diffusion of iron oxide nanoparticles in an osmotically disrupted cell culture model of the blood-brain barrier. Int J Nanomedicine 9(1):3013–3026CrossRefGoogle Scholar
  34. Szalay B, Tátrai E, Nyírő G, Vezér T, Dura G (2012) Potential toxic effects of iron oxide nanoparticles in in vivo and in vitro experiments. J Appl Toxicol 32(6):446–453. Available at.  https://doi.org/10.1002/jat.1779 CrossRefGoogle Scholar
  35. Umarao P, Bose S, Bhattacharyya S, Kumar A, Jain S (2016) Neuroprotective potential of superparamagnetic iron oxide nanoparticles along with exposure to electromagnetic field in 6-OHDA rat model of Parkinson’s disease. J Nanosci Nanotechnol 16(1):261–269CrossRefGoogle Scholar
  36. Vayenas DV, Repanti M, Vassilopoulos A, Papanastasiou DA (1998) Influence of iron overload on manganese, zinc, and copper concentration in rat tissues in vivo: study of liver, spleen, and brain. Int J Clin Lab Res 28(3):183–186 Available at: http://www.ncbi.nlm.nih.gov/pubmed/9801930 CrossRefGoogle Scholar
  37. Wang L, Wang L, Ding W, Zhang F (2010) Acute toxicity of ferric oxide and zinc oxide nanoparticles in rats. J Nanosci Nanotechnol 10:8617–8624CrossRefGoogle Scholar
  38. Wáng YXJ, Idée J-M (2017) A comprehensive literatures update of clinical researches of superparamagnetic resonance iron oxide nanoparticles for magnetic resonance imaging. Quant Imaging Med Surg 7(1):88–122 Available at: http://qims.amegroups.com/article/view/13786/14098 CrossRefGoogle Scholar
  39. Yah CS, Iyuke SE, Simate GS (2012) A review of nanoparticles toxicity and their routes of exposures. Iran J Pharm Sci 8(1):299–314Google Scholar
  40. Yarjanli Z, Ghaedi K, Esmaeili A, Rahgozar S, Zarrabi A (2017) Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation. BMC Neurosci 18(1):51. Available at:.  https://doi.org/10.1186/s12868-017-0369-9 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Dalel Askri
    • 1
    • 2
  • Souhir Ouni
    • 2
  • Said Galai
    • 3
  • Josiane Arnaud
    • 4
  • Benoit Chovelon
    • 4
  • Sylvia G. Lehmann
    • 5
  • Nathalie Sturm
    • 6
  • Mohsen Sakly
    • 2
  • Michel Sève
    • 1
  • Salem Amara
    • 2
  1. 1.University of Grenoble Alpes, PROMETHEE Proteomic Platform, IBP, CHU Grenoble Alpes, LBFA Inserm U1055 and BEeSyGrenobleFrance
  2. 2.Fac. Sciences of Bizerte, Unit of Integrated PhysiologyUniversity of CarthageBizerteTunisia
  3. 3.Laboratory of Clinical Biology, National Institute of NeurologyUniversity of Tunis El ManarTunisTunisia
  4. 4.Unit of Hormonal and Nutritional Biochemistry, Department of Biology, Toxicology, Pharmacology, CHU Grenoble AlpesGrenobleFrance
  5. 5.Univ. Grenoble Alpes, ISTerreGrenobleFrance
  6. 6.Department of Pathological Anatomy and CytologyCHU Grenoble AlpesGrenobleFrance

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