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Surface coatings alter transcriptional responses to silver nanoparticles following oral exposure.

ABSTRACT: Silver nanoparticles (AgNPs) are used in food packaging materials, dental care products and other consumer goods and can result in oral exposure. To determine whether AgNP coatings modulate transcriptional responses to AgNP exposure, we exposed mice orally to 20 nm citrate (cit)-coated AgNPs (cit-AgNPs) or polyvinylpyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) at a 4 mg/kg dose for 7 consecutive days and analyzed changes in the expression of protein-coding genes and long noncoding RNAs (lncRNAs), a new class of regulatory RNAs, in the liver. We identified unique and common expression signatures of protein-coding and lncRNA genes, altered biological processes and signaling pathways, and coding-non-coding gene interactions for cit-AgNPs and PVP-AgNPs. Commonly regulated genes comprised only about 10 and 20 percent of all differentially expressed genes in PVP-AgNP and cit-AgNP exposed mice, respectively. Commonly regulated biological processes included glutathione metabolic process and cellular oxidant detoxification. Commonly regulated pathways included Keap-Nrf2, PPAR, MAPK and IL-6 signaling pathways. The coding-non-coding gene co-expression analysis revealed that protein-coding genes were co-expressed with a variable number of lncRNAs ranging from one to twenty three and may share functional roles with the protein-coding genes. PVP-AgNP exposure induced a more robust transcriptional response than cit-AgNP exposure characterized by more than two-fold higher number of differentially expressed both protein- coding and lncRNA genes. Our data demonstrate that the surface coating strongly modulates the spectrum and the number of differentially expressed genes after oral AgNP exposure. On the other hand, our data suggest that AgNP exposure can alter drug and chemical sensitivity, metabolic homeostasis and cancer risk irrespective of the coating type, warranting further investigations.

SUBMITTER: Nallanthighal S

PROVIDER: S-EPMC7453744 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Surface coatings alter transcriptional responses to silver nanoparticles following oral exposure.

Nallanthighal Sameera S Tierney Lukas L Cady Nathaniel C NC Murray Thomas M TM Chittur Sridar V SV Reliene Ramune R

NanoImpact 20191224

Silver nanoparticles (AgNPs) are used in food packaging materials, dental care products and other consumer goods and can result in oral exposure. To determine whether AgNP coatings modulate transcriptional responses to AgNP exposure, we exposed mice orally to 20 nm citrate (cit)-coated AgNPs (cit-AgNPs) or polyvinylpyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) at a 4 mg/kg dose for 7 consecutive days and analyzed changes in the expression of protein-coding genes and long noncoding RNAs (lncRNAs), a ...[more]

PMID: 32864508

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Project description:BackgroundThe study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials.ResultsAgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG) staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM), nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver.ConclusionsThe results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver granules containing selenium and sulfur in the intestinal wall of rats exposed to either of the silver forms suggests a common mechanism of their formation. Additional studies however, are needed to gain further insight into the underlying mechanisms of the granule formation, and to clarify whether AgNPs dissolve in the gastrointestinal system and/or become absorbed and translocate as intact nanoparticles to organs and tissues.

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Surface coatings alter transcriptional responses to silver nanoparticles following oral exposure.

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Surface coatings alter transcriptional responses to silver nanoparticles following oral exposure.

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