Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013 Hsinchu, Taiwan.
Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, 30013 Hsinchu, Taiwan.
Toxicol Lett. 2014 Jun 5;227(2):84-90. doi: 10.1016/j.toxlet.2014.03.014. Epub 2014 Apr 2.
With the increasing prevalence of silver nanoparticles (AgNPs) in various products, whether such AgNPs will introduce new injury mechanisms from new pathologies remains to be determined. From the toxicokinetic viewpoint, it is vital to have in-depth knowledge of their in vivo transport kinetics and extravasation phenomenon. By combining push-pull perfusion sampling, in-tube solid phase extraction, and inductively coupled plasma mass spectrometry, we used an in vivo push-pull-based continuous monitoring system to investigate in vivo transport kinetics of extracellular AgNPs in living rat liver with a detection limit and temporal resolution of 0.64μgL(-1) and 10min, respectively. Before administration into living rats, the pre-incubation in DMEM with 10% FBS for 8h was adopted as the optimized exposure condition for the used AgNPs. After repeated-dose treatments, we observed a higher concentration of AgNPs in the liver extracellular space, suggesting that AgNP clearance by the reticuloendothelial system (RES) may be blocked by a prior administration of AgNPs. Future studies on AgNP distribution in different liver compartments (blood stream, extracellular space and Kupffer cells/hepatocytes) are necessary for defining the risks and benefits of AgNP applications.
随着银纳米粒子（AgNPs）在各种产品中的广泛应用，这些 AgNPs 是否会带来新的病理损伤机制仍有待确定。从毒代动力学的角度来看，深入了解它们在体内的转运动力学和渗出现象至关重要。本研究采用推挽式灌流采样、内管固相萃取和电感耦合等离子体质谱联用技术，利用基于推挽式的体内连续监测系统，以检测限和时间分辨率分别为 0.64μgL(-1)和 10min 的水平，研究了活体大鼠肝脏中细胞外 AgNPs 的体内转运动力学。在将 AgNPs 注入活体大鼠之前，采用在含 10%胎牛血清的 DMEM 中孵育 8h 的预处理方式作为所使用的 AgNPs 的优化暴露条件。经过重复剂量处理后，我们观察到肝脏细胞外空间中 AgNPs 的浓度更高，这表明 AgNP 被网状内皮系统（RES）清除的过程可能会被预先给予的 AgNPs 所阻断。未来有必要对 AgNP 在不同肝脏隔室（血流、细胞外空间和库普弗细胞/肝细胞）中的分布进行研究，以确定 AgNP 应用的风险和益处。
