Institute of Environmental Medicine for Green Chemistry, Dongguk University Biomedi Campus, Ilsandong-gu, Goyang-si, Republic of Korea,
Department of Life Science, Dongguk University Biomedi Campus, Ilsandong-gu, Goyang-si, Republic of Korea,
Int J Nanomedicine. 2019 Jan 8;14:393-405. doi: 10.2147/IJN.S174515. eCollection 2019.
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.
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).
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.
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.
Our investigation highlights the risk associated with a single cAgNP exposure with unrepaired damage persisting for at least a month.
银纳米粒子（AgNPs）广泛应用于工业和家庭应用，引起了人们对其在人类安全性的关注。用稳定剂包覆的 AgNPs 所带来的风险仍不清楚，评估其毒性对于了解其在各种应用中使用所涉及的安全问题至关重要。
我们旨在通过几项毒性测试和转录组分析，研究单次静脉注射兔耳静脉柠檬酸包覆的银纳米粒子（cAgNPs）后 7 和 28 天肝脏组织的长期毒性（n=4）。
本研究中使用的 cAgNPs 为 20%（w/v）水溶液，其尺寸通过透射电子显微镜测量为 7.9±0.95nm。动物实验是根据良好实验室规范的原则进行的。
我们的结果表明，由于单次暴露于 cAgNPs，肝脏组织的结构和功能被破坏。此外，体内彗星试验显示，单次注射后 4 周内肝脏组织的遗传毒性未得到修复，提示 cAgNPs 具有潜在的致癌作用。在我们的转录组分析中，在单次 cAgNP 注射后 28 天，总共发现 244 个基因的表达存在差异。使用 Pathway Studio 和 Ingenuity Pathway Analysis 工具对这些基因进行仔细 curated 途径分析，揭示了主要的分子网络对 cAgNP 暴露的反应，并表明这些基因与炎症、肝毒性和癌症高度相关。分子验证表明了评估累积 cAgNPs 毒性的潜在生物标志物。
我们的研究强调了单次 cAgNP 暴露所带来的风险，这种损伤在至少一个月内仍未得到修复。
