Zinc protects the rat brain from damage induced by 24 h exposure to silver nanoparticles

  • Samuel Salazar-García
  • Norma Laura Delgado-Buenrostro
  • Juan Carlos Rodríguez-Escamilla
  • Guillermo Davalos-Rivas
  • Yolanda Irasema Chirino
  • Claudia G. Castillo Martín del Campo
  • Gabriel A. Martínez-Castañón
  • Juan Manuel Vargas-Morales
  • Carmen GonzalezEmail author
Research Paper


Silver nanoparticles (AgNPs) have been widely employed due to their antimicrobial properties; however, several studies sustain that AgNPs can induce brain damage, like the blood–brain barrier (BBB) disruption. Among the BBB defense mechanisms, the metallothioneins (MTs), a collection of proteins that regulate intracellular levels of zinc (Zn), play an important role. The goal of this work was to investigate whether the brain damage caused by an intraperitoneal administration of AgNPs (15 mg/ g body weight) at the level of the BBB permeability disruption, damage of the brain tissue, and systemic inflammation could be prevented by 24 h of previous treatment with Zn (27 mg/kg body weight). Evans blue (EB) extravasation, modification of claudin-5 expression, alterations on MTs, N-cadherin expression, and systemic inflammation were evaluated. Our results show that AgNPs induce BBB damage by increasing EB extravasation and decreasing claudin-5 expression, associated with overexpression of MTs, effects that were related with systemic inflammation, evidenced by the increase of granulocytes. Zn pretreatment partially prevented the BBB permeability from the damage induced by AgNPs, whereas the MTs expression and granulocytes count exhibited a reversal effect, suggesting that the effect of Zn could be related with the BBB regulation process. The rat brain histological analysis confirmed that pretreatment with Zn prevented at least in part the toxic effect of AgNPs. This work provides relevant information about the role of Zn as a protectant against the noxious effects of AgNPs upon the rat brain physiology.


Silver nanoparticles Brain Blood–brain barrier Metallothioneins Zinc Protection Nanomedicine 



Bicinchoninic acid


Blood–brain barrier


Central nervous system


Dynamic light scattering


Evans blue










Glyceraldehyde-3-phosphate dehydrogenase
















Red blood cells


Silver nanoparticles


Silver nitrate


Tight junctions


Transmission electron microscopy


White blood cells




Zinc chloride



The authors thank to Francisco Javier Torres de la Rosa, José Fernando García de la Cruz, and Edgar Rangel Lopez for their technical assistance. This work was supported by the grant C16-PIFI-09-08.08 and the National Council of Science and Technology Project 268769. Samuel Salazar was a recipient of a scholarship from CONACyT (342918).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Samuel Salazar-García
    • 1
    • 2
  • Norma Laura Delgado-Buenrostro
    • 3
  • Juan Carlos Rodríguez-Escamilla
    • 3
  • Guillermo Davalos-Rivas
    • 1
    • 2
  • Yolanda Irasema Chirino
    • 3
  • Claudia G. Castillo Martín del Campo
    • 4
  • Gabriel A. Martínez-Castañón
    • 5
  • Juan Manuel Vargas-Morales
    • 1
  • Carmen Gonzalez
    • 1
    • 2
    Email author
  1. 1.Facultad de Ciencias QuimicasUniversidad Autonoma de San Luis PotosiSan Luis PotosiMexico
  2. 2.Centro de Investigacion en Ciencias de la Salud y BiomedicinaUniversidad Autonoma de San Luis PotosiSan Luis PotosiMexico
  3. 3.Unidad de Biomedicina, Facultad de Estudios Superiores IztacalaUniversidad Nacional Autonoma de MexicoEstado de MexicoMexico
  4. 4.Facultad de MedicinaUniversidad Autonoma de San Luis PotosiSan Luis PotosiMexico
  5. 5.Facultad de EstomatologiaUniversidad Autónoma de San Luis PotosiSan Luis PotosiMexico

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