Heriot-Watt University, School of Life Sciences, Edinburgh, EH14 4AS, UK.
BMC Nephrol. 2013 Apr 25;14:96. doi: 10.1186/1471-2369-14-96.
It has been shown that nanomaterials (NMs) are able to translocate to secondary tissues one of the important being the kidneys. Oxidative stress has been implicated as a possible mechanism for NM toxicity, hence effects on the human renal proximal tubule epithelial cells (HK-2) treated with a panel of engineered nanomaterials (NMs) consisting of two zinc oxide particles (ZnO - coated - NM 110 and uncoated - NM 111), two multi walled carbon nanotubes (MWCNT) (NM 400 and NM 402), one silver (NM 300) and five TiO2 NMs (NM 101, NRCWE 001, 002, 003 and 004) were evaluated.
In order to assess the toxicological impact of the engineered NMs on HK-2 cells - WST-1 cytotoxicity assay, FACSArray, HE oxidation and the comet assays were utilised. For statistical analysis, the experimental values were compared to their corresponding controls using an ANOVA with Tukey's multiple comparison.
We found the two ZnO NMs (24 hr LC50 - 2.5 μg/cm2) and silver NM (24 hr LC50 - 10 μg/cm2) were highly cytotoxic to the cells. The LC50 was not attained in the presence of any of the other engineered nanomaterials (up to 80 μg/cm2). All nanomaterials significantly increased IL8 and IL6 production. Meanwhile no significant change in TNF-α or MCP-1 was detectable. The most notable increase in ROS was noted following treatment with the Ag and the two ZnO NMs. Finally, genotoxicity was measured at sub-lethal concentrations. We found a small but significant increase in DNA damage following exposure to seven of the ten NMs investigated (NM 111, NRCWE 001 and NRCWE 003 being the exception) with this increase being most visible following exposure to Ag and the positively charged TiO2.
While the NMs could be categorised as low and highly cytotoxic, sub-lethal effects such as cytokine production and genotoxicity were observed with some of the low toxicity materials.
已经证明纳米材料（NMs）能够转移到次级组织中，其中一个重要的组织是肾脏。氧化应激已被认为是纳米材料毒性的一种可能机制，因此，用一组工程纳米材料（NMs）处理人肾近端小管上皮细胞（HK-2）的效果，这些 NMs 包括两种氧化锌颗粒（涂覆的 NM 110 和未涂覆的 NM 111）、两种多壁碳纳米管（MWCNT）（NM 400 和 NM 402）、一种银（NM 300）和五种 TiO2 NMs（NM 101、NRCWE 001、002、003 和 004）进行了评估。
为了评估工程 NMs 对 HK-2 细胞的毒理学影响，使用了 WST-1 细胞毒性测定法、FACSArray、HE 氧化和彗星测定法。为了进行统计分析，将实验值与相应的对照值进行比较，使用方差分析和 Tukey 多重比较。
我们发现两种 ZnO NMs（24 小时 LC50-2.5 μg/cm2）和银 NM（24 小时 LC50-10 μg/cm2）对细胞具有高度细胞毒性。在任何其他工程纳米材料存在的情况下，均未达到 LC50（高达 80 μg/cm2）。所有纳米材料均显著增加了 IL8 和 IL6 的产生。同时，TNF-α或 MCP-1 没有明显变化。在用 Ag 和两种 ZnO NMs 处理后，ROS 的增加最为明显。最后，在亚致死浓度下测量了遗传毒性。我们发现，在暴露于十种 NMs 中的七种后，DNA 损伤略有但显著增加（NM 111、NRCWE 001 和 NRCWE 003 除外），在暴露于 Ag 和带正电荷的 TiO2 后，这种增加最为明显。
虽然这些 NMs 可以归类为低细胞毒性和高细胞毒性，但在一些低毒性材料中观察到了亚致死效应，如细胞因子产生和遗传毒性。
