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Assessment of in vivo genotoxicity of citrated-coated silver nanoparticles via transcriptomic analysis of rabbit liver tissue

Authors Kim YJ, Rahman MM, Lee SM, Kim JM, Park K, Kang JH, Seo YR

Received 17 May 2018

Accepted for publication 27 July 2018

Published 8 January 2019 Volume 2019:14 Pages 393—405

DOI https://doi.org/10.2147/IJN.S174515

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster


Yeo Jin Kim,1,2 Md Mujibur Rahman,1 Sang Min Lee,2 Jung Min Kim,3 Kwangsik Park,4 Joo-Hyon Kang,5 Young Rok Seo1,2

1Institute of Environmental Medicine for Green Chemistry, Dongguk University Biomedi Campus, Ilsandong-gu, Goyang-si, Republic of Korea; 2Department of Life Science, Dongguk University Biomedi Campus, Ilsandong-gu, Goyang-si, Republic of Korea; 3Genoplan Korea, Inc., Seocho-gu, Seoul, Republic of Korea; 4College of Pharmacy, Dongduk Women’s University, Seongbuk-gu, Seoul, Republic of Korea; 5Department of Civil & Environmental Engineering, Dongguk University, Jung-gu, Seoul, Republic of Korea

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.

Keywords:
nanotoxicity, liver toxicity, prolonged tissue damage, differentially expressed genes, molecular pathway analysis

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