Skip to main content
Log in

Silver nanoparticles (AgNPs) and zinc chloride (ZnCl2) exposure order determines the toxicity in C6 rat glioma cells

  • Research paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

Silver nanoparticles (AgNPs) induced specific cell toxicity, and they are used as a tool for the study of several pathologies such as cancer. This work aimed to elucidate the toxic effect of < 10-nm silver nanoparticles (AgNPs) and zinc chloride (ZnCl2) in different administration orders on C6 rat glioma cells, as a biological model of study. C6 rat glioma cells were exposed to increasing concentrations of AgNPs (10–100 μg/mL) in the presence or absence of ZnCl2 (10–50 μg/mL) for 24 h. AgNPs or ZnCl2 as separate treatments decreased C6 rat glioma cell viability by 21% and 13%, respectively, versus the control, using the MTT assay. The administration of AgNPs (50 μg/mL) in the presence of ZnCl2 (10–50 μg/mL) was performed under two conditions: as pretreatment and as concomitant administration; both of them showed a significant decrease in the cell viability, around 30% and 90%, respectively. It was the concomitant treatment, which exerted the most significant effect on the viability decrease. We also observed that 24-h exposure to AgNPs increased cell populations (40%) in stages G0/G1 of the cell cycle, and decreased the number of cells (60%) in stages G2/M. However, in the concomitant treatment, as well as during induced cell death, the ZnCl2 pretreatment and concomitant treatment modified the cycle, increasing the S phase by 10%, suggesting that zinc (Zn) could be an essential regulator of the C6 rat glioma cell damage induced by AgNPs. This study will allow us to understand the mechanisms of cellular response to AgNPs, for the eventual study of these particles as a potential agent against cancer, such as glioblastoma multiforme.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Alphandéry E (2020) Nano-therapies for glioblastoma treatment. Cancers. 12(1):242

    Article  Google Scholar 

  • Asharani P, Wu YL, Gong Z, Valiyaveettil S (2008) Toxicity of silver nanoparticles in zebrafish models. Nanotechnology 19(25):255102

    Article  CAS  Google Scholar 

  • AshaRani P, Low Kah Mun G, Hande MP, Valiyaveettil S (2009) Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 3(2):279–290

    Article  CAS  Google Scholar 

  • Bashandy SAE-M, Omara EAA, Ebaid H, Amin MM, Soliman MS (2016) Role of zinc as an antioxidant and anti-inflammatory to relieve cadmium oxidative stress induced testicular damage in rats. Asian Pac J Trop Biomed 6(12):1056–1064

    Article  Google Scholar 

  • Beljanski M, Crochet S (1994) Differential effects of ferritin, calcium, zinc, and gallic acid on in vitro proliferation of human glioblastoma cells and normal astrocytes. J Lab Clin Med 123(4):547–555

    CAS  Google Scholar 

  • Bopp SK, Lettieri T (2008) Comparison of four different colorimetric and fluorometric cytotoxicity assays in a zebrafish liver cell line. BMC Pharmacol 8(1):8

    Article  Google Scholar 

  • Chasapis CT, Ntoupa P-SA, Spiliopoulou CA, Stefanidou ME (2020) Recent aspects of the effects of zinc on human health. Arch Toxicol 94:1–18

  • Chen W-Q, Cheng Y-Y, Zhao X-L, Li S-T, Hou Y, Hong Y (2006) Effects of zinc on the induction of metallothione in isoforms in hippocampus in stress rats. Exp Biol Med 231(9):1564–1568

    Article  CAS  Google Scholar 

  • Denizot F, Lang R (1986) Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89(2):271–277

    Article  CAS  Google Scholar 

  • Doblas S, He T, Saunders D, Pearson J, Hoyle J, Smith N, Lerner M, Towner RA (2010) Glioma morphology and tumor-induced vascular alterations revealed in seven rodent glioma models by in vivo magnetic resonance imaging and angiography. J Magn Reson Imaging 32(2):267–275

    Article  Google Scholar 

  • Espinosa-Cristobal L, Martinez-Castanon G, Loyola-Rodriguez J, Patino-Marin N, Reyes-Macias J, Vargas-Morales J et al (2013) Toxicity, distribution, and accumulation of silver nanoparticles in Wistar rats. J Nanopart Res 15(6):1702

    Article  Google Scholar 

  • Foldbjerg R, Dang DA, Autrup H (2011) Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch Toxicol 85(7):743–750

    Article  CAS  Google Scholar 

  • Fouad A, Hafez R (2018) The effects of silver ions and silver nanoparticles on cell division and expression of cdc2 gene in Allium cepa root tips. Biol Plant 62(1):166–172

    Article  CAS  Google Scholar 

  • Franciscato C, Moraes-Silva L, Duarte F, Oliveira C, Ineu R, Flores E et al (2011) Delayed biochemical changes induced by mercury intoxication are prevented by zinc pre-exposure. Ecotoxicol Environ Saf 74(3):480–486

    Article  CAS  Google Scholar 

  • Gurunathan S, Han JW, Eppakayala V, Jeyaraj M, Kim J-H (2013) Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells. Biomed Res Int 2013:1–10

    Article  Google Scholar 

  • Jeyaraj M, Sathishkumar G, Sivanandhan G, MubarakAli D, Rajesh M, Arun R, Kapildev G, Manickavasagam M, Thajuddin N, Premkumar K, Ganapathi A (2013) Biogenic silver nanoparticles for cancer treatment: an experimental report. Colloids Surf B: Biointerfaces 106:86–92

    Article  CAS  Google Scholar 

  • Kauppinen TM, Higashi Y, Suh SW, Escartin C, Nagasawa K, Swanson RA (2008) Zinc triggers microglial activation. J Neurosci 28(22):5827–5835

    Article  CAS  Google Scholar 

  • Khan I, Saeed K, Khan I (2019) Nanoparticles: properties, applications and toxicities. Arab J Chem 12(7):908–931

    Article  CAS  Google Scholar 

  • Kim TH, Kim M, Park HS, Shin US, Gong MS, Kim HW (2012) Size-dependent cellular toxicity of silver nanoparticles. J Biomed Mater Res A 100(4):1033–1043

    Article  Google Scholar 

  • Liu W, Worms IAM, Herlin-Boime N, Truffier-Boutry D, Michaud-Soret I, Mintz E, Vidaud C, Rollin-Genetet F (2017) Interaction of silver nanoparticles with metallothionein and ceruloplasmin: impact on metal substitution by Ag(i), corona formation and enzymatic activity. Nanoscale 9(19):6581–6594

    Article  CAS  Google Scholar 

  • Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109

    Article  Google Scholar 

  • Luther EM, Schmidt MM, Diendorf J, Epple M, Dringen R (2012) Upregulation of metallothioneins after exposure of cultured primary astrocytes to silver nanoparticles. Neurochem Res 37(8):1639–1648

    Article  CAS  Google Scholar 

  • Mahmoudi M, Azadmanesh K, Shokrgozar MA, Journeay WS, Laurent S (2011) Effect of nanoparticles on the cell life cycle. Chem Rev 111(5):3407–3432

    Article  CAS  Google Scholar 

  • Maret W (2013) Zinc biochemistry: from a single zinc enzyme to a key element of life. Adv Nutr 4(1):82–91

    Article  CAS  Google Scholar 

  • Mikhailova V, Gulaia V, Tiasto V, Rybtsov S, Yatsunskaya M, Kagansky A (2018) Towards an advanced cell-based in vitro glioma model system. AIMS Genet 5(2):91–112

    Article  Google Scholar 

  • Moreno-Vilet L, Garcia-Hernandez M, Delgado-Portales R, Corral-Fernandez N, Cortez-Espinosa N, Ruiz-Cabrera M et al (2014) In vitro assessment of agave fructans (Agave salmiana) as prebiotics and immune system activators. Int J Biol Macromol 63:181–187

    Article  CAS  Google Scholar 

  • Ostrovsky S, Kazimirsky G, Gedanken A, Brodie C (2009) Selective cytotoxic effect of ZnO nanoparticles on glioma cells. Nano Res 2(11):882–890

    Article  CAS  Google Scholar 

  • Perrin L, Roudeau S, Carmona A, Domart F, Petersen JD, Bohic S et al (2017) Zinc and copper effects on stability of tubulin and actin networks in dendrites and spines of hippocampal neurons. ACS Chem Neurosci 8(7):1490–1499

    Article  CAS  Google Scholar 

  • Prasad AS, Kucuk O (2002) Zinc in cancer prevention. Cancer Metastasis Rev 21(3–4):291–295

    Article  CAS  Google Scholar 

  • Priyadharshini RI, Prasannaraj G, Geetha N, Venkatachalam P (2014) Microwave-mediated extracellular synthesis of metallic silver and zinc oxide nanoparticles using macro-algae (Gracilaria edulis) extracts and its anticancer activity against human PC3 cell lines. Appl Biochem Biotechnol 174(8):2777–2790

    Article  CAS  Google Scholar 

  • Puca R, Nardinocchi L, Porru M, Simon AJ, Rechavi G, Leonetti C, Givol D, D’Orazi G (2011) Restoring p53 active conformation by zinc increases the response of mutant p53 tumor cells to anticancer drugs. Cell Cycle 10(10):1679–1689

    Article  CAS  Google Scholar 

  • Ruttkay-Nedecky B, Nejdl L, Gumulec J, Zitka O, Masarik M, Eckschlager T, Stiborova M, Adam V, Kizek R (2013) The role of metallothionein in oxidative stress. Int J Mol Sci 14(3):6044–6066

    Article  CAS  Google Scholar 

  • Salazar-García S, Silva-Ramírez AS, Ramirez-Lee MA, Rosas-Hernandez H, Rangel-López E, Castillo CG, Santamaría A, Martinez-Castañon GA, Gonzalez C (2015) Comparative effects on rat primary astrocytes and C6 rat glioma cells cultures after 24-h exposure to silver nanoparticles (AgNPs). J Nanopart Res 17(11):450

    Article  Google Scholar 

  • Silva-Ramirez AS, Castillo CG, Navarro-Tovar G, Gonzalez-Sanchez HM, Rocha-Uribe A, Gonzalez-Chavez MM et al (2018) Bioactive isomers of conjugated linoleic acid inhibit the survival of malignant glioblastoma cells but not primary astrocytes. Eur J Lipid Sci Technol 120(11):1700454

    Article  Google Scholar 

  • Specification PA (2007) Terminology for nanomaterials. British Standards Institute, London

    Google Scholar 

  • Sukhanova A, Bozrova S, Sokolov P, Berestovoy M, Karaulov A, Nabiev I (2018) Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale Res Lett 13(1):44

    Article  Google Scholar 

  • Urbańska K, Pająk B, Orzechowski A, Sokołowska J, Grodzik M, Sawosz E, Szmidt M, Sysa P (2015) The effect of silver nanoparticles (AgNPs) on proliferation and apoptosis of in ovo cultured glioblastoma multiforme (GBM) cells. Nanoscale Res Lett 10(1):98

    Article  Google Scholar 

  • Zhang T, Wang L, Chen Q, Chen C (2014) Cytotoxic potential of silver nanoparticles. Yonsei Med J 55(2):283–291

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Samuel Salazar was the recipient of scholarships from CONACyT (342918). And CONACYT-SINANOTOX PN-2017-01-4710, recipient: Carmen González PhD.

Funding

This work was supported by the grant C16-PIFI-09-08.08.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carmen Gonzalez.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salazar-García, S., García-Rodrigo, J.F., Martínez-Castañón, G.A. et al. Silver nanoparticles (AgNPs) and zinc chloride (ZnCl2) exposure order determines the toxicity in C6 rat glioma cells. J Nanopart Res 22, 253 (2020). https://doi.org/10.1007/s11051-020-04984-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-020-04984-7

Keywords

Navigation