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Abstract
Background
Silver nanoparticles (AgNPs) are widely used in industrial and household applications, arousing concern regarding their safety in humans. The risks posed by stabilizer-coated AgNPs continue to be unclear, and assessing their toxicity is for an understanding of the safety issues involved in their use in various applications.
Purpose
We aimed to investigated the long-term toxicity of citrate-coated silver nanoparticles (cAgNPs) in liver tissue using several toxicity tests and transcriptomic analysis at 7 and 28 days after a single intravenous injection into rabbit ear veins (n=4).
Materials and methods
The cAgNPs used in this study were in the form of a 20% (w/v) aqueous solution, and their size was 7.9±0.95 nm, measured using transmission electron microscopy. The animal experiments were performed based on the principles of good laboratory practice.
Results
Our results showed that the structure and function of liver tissue were disrupted due to a single exposure to cAgNPs. In addition, in vivo comet assay showed unrepaired genotoxicity in liver tissue until 4 weeks after a single injection, suggesting a potential carcinogenic effect of cAgNPs. In our transcriptomic analysis, a total of 244 genes were found to have differential expression at 28 days after a single cAgNP injection. Carefully curated pathway analysis of these genes using Pathway Studio and Ingenuity Pathway Analysis tools revealed major molecular networks responding to cAgNP exposure and indicated a high correlation of the genes with inflammation, hepatotoxicity, and cancer. Molecular validation suggested potential biomarkers for assessing the toxicity of accumulated cAgNPs.
Conclusion
Our investigation highlights the risk associated with a single cAgNP exposure with unrepaired damage persisting for at least a month.
Acknowledgments
This research was supported by a grant (14CTAP-C086804-01) from the Technology Advancement Research Program funded by the Ministry of Land, Infrastructure and Transport of the Korean government. This work was also supported by a grant (NIER-SP2014-053-P10) from the National Institute of Environmental Research (NIER) and by a grant (2016001360009) funded by the Ministry of Environment of the Republic of Korea.
Disclosure
The authors report no conflicts of interest in this work.