Ammendolia Maria Grazia, Iosi Francesca, Maranghi Francesca, Tassinari Roberta, Cubadda Francesco, Aureli Federica, Raggi Andrea, Superti Fabiana, Mantovani Alberto, De Berardis Barbara
Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, Italy.
Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, Italy.
Food Chem Toxicol. 2017 Apr;102:63-75. doi: 10.1016/j.fct.2017.01.031. Epub 2017 Jan 31.
The present study investigated potential modulatory effects of low doses of nano-sized titanium dioxide (TiO) on intestinal cells in vivo and in vitro. After short-term exposure to TiO nanoparticles in rats, histopathological analysis of intestinal tissues indicated a gender-specific effect with increased length of intestinal villi in male rats only. Moreover the intestinal tissue showed nanoparticle deposition as revealed by ICP-MS determination of titanium. Increased serum testosterone levels were also detected. Considering the male-specific effects detected in vivo, the TiO nanoparticle interaction with intestinal cells was further characterized in vitro and the modulating effect of testosterone and a hormone-induced growth factor, namely Insulin-like Growth Factor 1 (IGF-1), was also assessed. Cytotoxicity assays and analysis of Reactive Oxygen Species (ROS) production showed neither cellular alteration nor oxidative stress for nanoparticles at low concentrations, even though they were able to penetrate intestinal cells, as revealed by electron microscopy. Cell treatments with nanoparticles in association with testosterone or IGF-1 showed increased cell proliferation, compared to nanoparticles or testosterone/IGF-1 alone. Since long-term intake of TiO nanoparticles at low doses is a relevant scenario for human exposure, attention should be given to the potential modulating activity of this nanomaterial on cell proliferation.
本研究调查了低剂量纳米级二氧化钛（TiO₂）在体内和体外对肠道细胞的潜在调节作用。在大鼠短期暴露于TiO₂纳米颗粒后，肠道组织的组织病理学分析表明存在性别特异性效应，仅雄性大鼠的肠绒毛长度增加。此外，通过电感耦合等离子体质谱法测定钛含量，发现肠道组织中有纳米颗粒沉积。还检测到血清睾酮水平升高。考虑到在体内检测到的雄性特异性效应，进一步在体外对TiO₂纳米颗粒与肠道细胞的相互作用进行了表征，并评估了睾酮和一种激素诱导的生长因子，即胰岛素样生长因子1（IGF-1）的调节作用。细胞毒性试验和活性氧（ROS）产生分析表明，低浓度纳米颗粒既未引起细胞改变，也未导致氧化应激，尽管电子显微镜显示它们能够穿透肠道细胞。与单独的纳米颗粒或睾酮/IGF-1相比，纳米颗粒与睾酮或IGF-1联合处理细胞显示细胞增殖增加。由于长期低剂量摄入TiO₂纳米颗粒是人类暴露的一种相关情况，应关注这种纳米材料对细胞增殖的潜在调节活性。
