Dipartimento di Medicina Sperimentale, Università degli Studi della Campania Luigi Vanvitelli, Napoli, Italy.
Istituto di Scienze dell'Alimentazione, Consiglio Nazionale delle Ricerche, Avellino, Italy.
Food Res Int. 2019 May;119:634-642. doi: 10.1016/j.foodres.2018.10.041. Epub 2018 Oct 12.
Titanium dioxide (TiO) is enclosed in many consumer products including pharmaceuticals, cosmetics, and foods. TiO (E171) is daily ingested as mixed nano- and submicron-sized particles since it is approved as a white colorant in Europe in a wide variety of food products, Noteworthy, the relevant risk assessment has never been satisfactorily concluded and growing alarms for human hazards deriving from TiO exposure are incrementally reported. The objective of the present study was to establish conceivable mechanisms by which nano-sized TiO particles affect physiological function of the intestinal epithelium layer. The well-established Caco-2 cell line differentiated for 21 days on permeable supports was used as a predictive model of the human intestinal mucosa to identify the biological response triggered by TiO particles. Exposure to 42 μg/mL TiO nanoparticles disrupted the tight junctions-permeability barrier with a prompt effect detectable after 4 h incubation time and wide effects on barrier integrity at 24 h. Transport and ultrastructural localization of TiO nanoparticles were determined by ICP-OES, TEM and ESI/EELS analysis, respectively. Nano-sized particles were efficiently internalized and preferentially entrapped by Caco-2 monolayers. Storage of TiO nanoparticles inside the cells affected enterocytes viability and triggered the production of pro-inflammatory cytokines, including TNF-α and IL-8. Taken together these data indicate that nano-sized TiO particles exert detrimental effects on the intestinal epithelium layer.
二氧化钛（TiO）被包含在许多消费品中，包括药品、化妆品和食品。TiO（E171）作为一种白色着色剂在欧洲被批准用于各种食品中，每天都会被摄入体内，其形式为混合的纳米级和亚微米级颗粒。值得注意的是，相关的风险评估从未得到令人满意的结论，并且越来越多的关于 TiO 暴露对人类危害的警报正在被报道。本研究的目的是建立可以想象的机制，通过这些机制，纳米级 TiO 颗粒会影响肠道上皮层的生理功能。我们使用已经建立的 Caco-2 细胞系，在可渗透的载体上分化 21 天，作为人类肠道黏膜的预测模型，以确定 TiO 颗粒引发的生物学反应。暴露于 42μg/mL 的 TiO 纳米颗粒会破坏紧密连接-通透性屏障，在 4 小时孵育时间后即可检测到即时效应，并且在 24 小时时对屏障完整性产生广泛影响。通过 ICP-OES、TEM 和 ESI/EELS 分析分别确定 TiO 纳米颗粒的转运和超微结构定位。纳米级颗粒被有效地内化，并被 Caco-2 单层优先捕获。TiO 纳米颗粒在细胞内的储存会影响肠细胞的活力，并触发促炎细胞因子（包括 TNF-α 和 IL-8）的产生。这些数据表明，纳米级 TiO 颗粒对肠道上皮层有不良影响。
