Department of Environmental Science and Policy (ESP), Università degli Studi di Milano, Milan, Italy.
Department of Biosciences (Department of Excellence 2018-2022), Università degli Studi di Milano, Milan, Italy.
J Appl Toxicol. 2021 Feb;41(2):291-302. doi: 10.1002/jat.4047. Epub 2020 Oct 27.
The use of CuO nanoparticles (NPs) has increased greatly and their potential effects on human health need to be investigated. Differentiated Caco-2 cells were treated from the apical (Ap) and the basolateral (Bl) compartment with different concentrations (0, 10, 50 and 100 μg/mL) of commercial or sonochemically synthesized (sono) CuO NPs. Sono NPs were prepared in ethanol (CuOe) or in water (CuOw), obtaining CuO NPs differing in size and shape. The effects on the Caco-2 cell barrier were assessed via transepithelial electrical resistance (TEER) evaluation just before and after 1, 2 and 24 hours of exposure and through the analysis of cytokine release and biomarkers of oxidative damage to proteins after 24 hours. Sono CuOe and CuOw NPs induced a TEER decrease with a dose-dependent pattern after Bl exposure. Conversely, TEER values were not affected by the Ap exposure to commercial CuO NPs and, concerning the Bl exposure, only the lowest concentration tested (10 μg/mL) caused a TEER decrease after 24 hours of exposure. An increased release of interleukin-8 was induced by sono CuO NPs after the Ap exposure to 100 μg/mL and by sono and commercial CuO after the Bl exposure to all the concentrations. No effects of commercial and sono CuO NPs on interleukin-6 (with the only exception of 100 μg/mL Bl commercial CuO) and tumor necrosis factor-α release were observed. Ap treatment with commercial and CuOw NPs was able to induce significant alterations on specific biomarkers of protein oxidative damage (protein sulfhydryl group oxidation and protein carbonylation).
氧化铜纳米粒子 (NPs) 的应用大大增加,需要研究其对人类健康的潜在影响。用不同浓度 (0、10、50 和 100μg/mL) 的商业或超声合成 (sono) CuO NPs 从顶 (Ap) 和基底 (Bl) 侧处理分化的 Caco-2 细胞。Sono NPs 分别在乙醇 (CuOe) 或水中 (CuOw) 制备,得到大小和形状不同的 CuO NPs。通过在暴露前和暴露后 1、2 和 24 小时测量跨上皮电阻 (TEER) 评估对 Caco-2 细胞屏障的影响,并在 24 小时后分析细胞因子释放和蛋白质氧化损伤生物标志物。超声 CuOe 和 CuOw NPs 经 Bl 暴露后,呈剂量依赖性模式,导致 TEER 下降。相反,商业 CuO NPs 的 Ap 暴露对 TEER 值没有影响,而就 Bl 暴露而言,只有在暴露 24 小时后测试的最低浓度 (10μg/mL) 才会导致 TEER 下降。超声 CuO NPs 在 Ap 暴露至 100μg/mL 后,以及超声和商业 CuO 在 Bl 暴露至所有浓度后,均诱导白细胞介素-8 释放增加。未观察到商业和超声 CuO NPs 对白细胞介素-6(商业 CuO 仅在 100μg/mL Bl 时有例外)和肿瘤坏死因子-α释放的影响。商业和 CuOw NPs 的 Ap 处理能够诱导蛋白质氧化损伤的特定生物标志物(蛋白质巯基氧化和蛋白质羰基化)发生显著变化。