Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, 109 Alexander Drive, B105-03, Durham, NC, 27711, USA.
Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, 109 Alexander Drive, B105-03, Durham, NC, 27711, USA.
Cell Biol Toxicol. 2019 Apr;35(2):129-145. doi: 10.1007/s10565-018-9445-x. Epub 2018 Oct 27.
The potential mammalian hepatotoxicity of nanomaterials was explored in dose-response and structure-activity studies in human hepatic HepG2 cells exposed to between 10 and 1000 μg/ml of five different CeO, three SiO, and one TiO-based particles for 3 days. Various biochemical parameters were then evaluated to study cytotoxicity, cell growth, hepatic function, and oxidative stress. Few indications of cytotoxicity were observed between 10 and 30 μg/ml. In the 100 to 300 μg/ml exposure range, a moderate degree of cytotoxicity was often observed. At 1000 μg/ml exposures, all but TiO showed a high degree of cytotoxicity. Cytotoxicity per se did not seem to fully explain the observed patterns of biochemical parameters. Four nanomaterials (all three SiO) decreased glucose 6-phosphate dehydrogenase activity with some significant decreases observed at 30 μg/ml. In the range of 100 to 1000 μg/ml, the activities of glutathione reductase (by all three SiO) and glutathione peroxidase were decreased by some nanomaterials. Decreased glutathione concentration was also found after exposure to four nanomaterials (all three nano SiO particles). In this study, the more responsive and informative assays were glucose 6-phosphate dehydrogenase, glutathione reductase, superoxide dismutase, lactate dehydrogenase, and aspartate transaminase. In this study, there were six factors that contribute to oxidative stress observed in nanomaterials exposed to hepatocytes (decreased glutathione content, reduced glucose 6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and increased catalase activities). With respect to structure-activity, nanomaterials of SiO were more effective than CeO in reducing glutathione content, glucose 6-phosphate dehydrogenase, glutathione reductase, and superoxide dismutase activities.
在人类 HepG2 细胞中进行了剂量反应和结构活性研究，以探索纳米材料对哺乳动物肝脏的潜在毒性。将五种不同的 CeO、三种 SiO 和一种 TiO 基颗粒分别暴露于 10 至 1000μg/ml 之间，持续 3 天。然后评估了各种生化参数以研究细胞毒性、细胞生长、肝功能和氧化应激。在 10 至 30μg/ml 之间观察到很少有细胞毒性的迹象。在 100 至 300μg/ml 的暴露范围内，通常观察到中度细胞毒性。在 1000μg/ml 的暴露下，除了 TiO 之外，所有颗粒都表现出高度的细胞毒性。细胞毒性本身似乎不能完全解释观察到的生化参数模式。四种纳米材料（三种 SiO）降低了葡萄糖 6-磷酸脱氢酶的活性，在 30μg/ml 时观察到一些显著降低。在 100 至 1000μg/ml 的范围内，三种 SiO 纳米材料降低了谷胱甘肽还原酶和谷胱甘肽过氧化物酶的活性。暴露于四种纳米材料（三种纳米 SiO 颗粒）后，谷胱甘肽浓度也降低。在这项研究中，葡萄糖 6-磷酸脱氢酶、谷胱甘肽还原酶、超氧化物歧化酶、乳酸脱氢酶和天冬氨酸转氨酶是更敏感和信息丰富的测定方法。在这项研究中，有六个因素导致了暴露于肝细胞的纳米材料中观察到的氧化应激（谷胱甘肽含量降低、葡萄糖 6-磷酸脱氢酶、谷胱甘肽还原酶、谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶活性增加）。就结构活性而言，SiO 纳米材料比 CeO 更有效地降低了谷胱甘肽含量、葡萄糖 6-磷酸脱氢酶、谷胱甘肽还原酶和超氧化物歧化酶的活性。
