Xue Y, Wang J, Huang Y, Gao X, Kong L, Zhang T, Tang M
1 Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210009, China.
2 Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009, China.
Hum Exp Toxicol. 2018 Dec;37(12):1293-1309. doi: 10.1177/0960327118769718. Epub 2018 Apr 16.
Silver nanoparticles are used in many commercial products in daily life. Exposure to nanosilver has hepatotoxic effects in animals. This study investigated the cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 ± 4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in HepG2 cells. Nanosilver, in doses of 20-160 μg mL for 24 and 48 h, reduced cell viability in a dose- and time-dependent manner and induced cell membrane leakage and mitochondria injury in both cell lines; these effects were more pronounced in HepG2 cells than in L02 cells. Intracellular oxidative stress was documented by reactive oxygen species (ROS) being generated in HepG2 cells but not in L02 cells, an effect possibly due to differential uptake of nanosilver by cancer cells and normal cells. In HepG2 cells, apoptosis was documented by finding that ROS triggered a decrease in mitochondrial membrane potential, an increase in cytochrome c release, activation of caspase 3 and caspase 9, and a decrease in the ratio of Bcl-2/Bax. Furthermore, nanosilver activated the Fas death receptor pathway by downregulation of nuclear factor-κB and activation of caspase 8 and caspase 3. These results suggest that apoptosis induced by nanosilver in HepG2 cells is mediated via a mitochondria-dependent pathway and the Fas death receptor pathway. These findings provide toxicological and mechanistic information that can help in assessing the effects of nanosilver in biological systems, including the potential for anticancer activities.
银纳米颗粒被用于日常生活中的许多商业产品。接触纳米银对动物具有肝毒性作用。本研究调查了聚维酮碘包被的纳米银（直径为23.44±4.92纳米）暴露于人类肝癌细胞系（HepG2）和正常肝细胞系（L02）时的细胞毒性，以及纳米银在HepG2细胞中诱导的分子机制。纳米银剂量为20 - 160μg/mL，处理24小时和48小时，以剂量和时间依赖性方式降低细胞活力，并在两种细胞系中诱导细胞膜渗漏和线粒体损伤；这些效应在HepG2细胞中比在L02细胞中更明显。通过在HepG2细胞中产生活性氧（ROS）而在L02细胞中未产生来证明细胞内氧化应激，这种效应可能是由于癌细胞和正常细胞对纳米银的摄取差异所致。在HepG2细胞中，通过发现ROS触发线粒体膜电位降低、细胞色素c释放增加、半胱天冬酶3和半胱天冬酶9激活以及Bcl-2/Bax比值降低来证明细胞凋亡。此外，纳米银通过下调核因子κB以及激活半胱天冬酶8和半胱天冬酶3激活Fas死亡受体途径。这些结果表明，纳米银在HepG2细胞中诱导的细胞凋亡是通过线粒体依赖性途径和Fas死亡受体途径介导的。这些发现提供了毒理学和机制信息，有助于评估纳米银在生物系统中的作用，包括抗癌活性的潜力。
