Repeated oral administration of low doses of silver in mice : tissue distribution and effects on central nervous system
Articolo
Data di Pubblicazione:
2021
Citazione:
Repeated oral administration of low doses of silver in mice : tissue distribution and effects on central nervous system / C. Recordati, M. De Maglie, C. Cella, S. Argentiere, S. Paltrinieri, S. Bianchessi, M. Losa, F. Fiordaliso, A. Corbelli, G. Milite, F. Aureli, M. D’Amato, A. Raggi, F. Cubadda, S. Soldati, C. Lenardi, E. Scanziani. - In: PARTICLE AND FIBRE TOXICOLOGY. - ISSN 1743-8977. - 18:1(2021 Jun 16), pp. 23.1-23.18. [10.1186/s12989-021-00418-x]
Abstract:
Background: Widespread use of silver in its different forms raises concerns about potential adverse effects after
ingestion, the main exposure route for humans. The aim of this study was to investigate in CD-1 (ICR) male mice
the tissue distribution and in vivo effects of 4-week oral exposure to 0.25 and 1 mg Ag/kg bw 10 nm citrate coated
silver nanoparticles (AgNPs) and 1 mg Ag/kg bw silver acetate (AgAc) at the end of treatment (EoT) and after 4
weeks of recovery.
Results: There were no treatment-related clinical signs and mortality, and no significant effects on body and organ
weights at the EoT and after recovery. Treatment-related changes in hematology and clinical chemistry were found
after recovery, the most relevant being a dose-dependent lymphopenia and increased triglycerides in AgNP-treated
mice, and increased levels of urea in all treated groups, associated with decreased albumin only in AgAc-treated
mice. At the EoT the highest silver concentration determined by Triple Quadrupole ICP-MS analysis was found in
the brain, followed by testis, liver, and spleen; much lower concentrations were present in the small intestine and
kidney. Tissue silver concentrations were slightly higher after exposure to AgAc than AgNPs and dose dependent
for AgNPs. After recovery silver was still present in the brain and testis, highlighting slow elimination. No
histopathological changes and absence of silver staining by autometallography were observed in the organs of
treated mice. At the EoT GFAP (astrocytes) immunoreactivity was significantly increased in the hippocampus of
AgNP-treated mice in a dose-dependent manner and Iba1 (microglial cells) immunoreactivity was significantly
increased in the cortex of 1 mg/kg bw AgNP-treated mice. After recovery, a significant reduction of Iba1 was
observed in the cortex of all treated groups. TEM analysis of the hippocampus revealed splitting of basement
membrane of the capillaries and swelling of astrocytic perivascular end-feet in 1 mg/kg bw AgNP- and AgActreated mice at the EoT.
Conclusions: Our study revealed accumulation and slow clearance of silver in the brain after oral administration of
10 nm AgNPs and AgAc at low doses in mice, associated with effects on glial cells and ultrastructural alterations of
the Blood-Brain Barrier.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Blood brain barrier; Central nervous system; Mouse; Oral administration; Silver acetate; Silver nanoparticles; Tissue distribution; Toxicity
Elenco autori:
C. Recordati, M. De Maglie, C. Cella, S. Argentiere, S. Paltrinieri, S. Bianchessi, M. Losa, F. Fiordaliso, A. Corbelli, G. Milite, F. Aureli, M. D’Amato, A. Raggi, F. Cubadda, S. Soldati, C. Lenardi, E. Scanziani
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