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The combined effect of food additive titanium dioxide and lipopolysaccharide on mouse intestinal barrier function after chronic exposure of titanium dioxide-contained feedstuffs
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2021-02-17 , DOI: 10.1186/s12989-021-00399-x
Yongliang Zhang 1 , Shumin Duan 1 , Ying Liu 2 , Yun Wang 1
Affiliation  

Up to 44% of particulates of food-grade titanium dioxide (TiO2) are in nanoscale, while the effect and combined effect of which with other substances on intestinal barrier haven’t been fully understood yet. This study is aimed to study the effect of two kinds of TiO2 nanoparticles (TiO2 NPs and TiO2 MPs) on intestinal barrier functions, to reveal the combined effect of TiO2 NPs and Lipopolysaccharide (LPS) on intestinal barrier. Male ICR mice were randomly divided into 18 groups (3 feed types * 3 exposure length * 2 LPS dosage) and were fed with normal or TiO2-mixed feed (containing 1% (mass fraction, w/w) TiO2 NPs or TiO2 MPs) for 1, 3, 6 months, followed by a single oral administration of 0 or 10 mg/(kg body weight) LPS. Four hours later, the transportation of TiO2, the intestinal barrier functions and the inflammatory response were evaluated. Both TiO2 notably increased the intestinal villi height / crypt depth ratios after 1 and 3 months of exposure, and increased the expression of ileal tight junction proteins (ZO-1 and occludin) after 1 month of exposure. After 6 months of exposure, TiO2 NPs led to reduced feed consumption, TiO2 MPs caused spare microvilli in small intestine and elevated Ti content in the blood cells. The intestinal permeability didn’t change in both TiO2 exposed groups. After LPS administration, we observed altered intestinal villi height / crypt depth ratios, lowered intestinal permeability (DAO) and upregulated expression of ileal ZO-1 in both (TiO2 +LPS) exposed groups. There are no significant changes of ileal or serum cytokines except for a higher serum TNF-α level in LPS treated group. The antagonistic effect was found between TiO2 NPs and LPS, but there are complicated interactions between TiO2 MPs and LPS. Long-term intake of food additive TiO2 could alter the intestinal epithelial structure without influencing intestinal barrier function. Co-exposure of TiO2 and LPS would enhance intestinal barrier function without causing notable inflammatory responses, and there is antagonistic effect between TiO2 NPs and LPS. All the minor effects observed might associate with the gentle exposure method where TiO2 being ingested with feed.

中文翻译:

食品添加剂二氧化钛和脂多糖对小鼠长期接触含二氧化钛饲料后肠道屏障功能的综合影响

高达 44% 的食品级二氧化钛 (TiO2) 颗粒是纳米级的,而其与其他物质对肠道屏障的作用和联合作用尚未完全了解。本研究旨在研究两种TiO2纳米颗粒(TiO2 NPs和TiO2 MPs)对肠道屏障功能的影响,以揭示TiO2 NPs和脂多糖(LPS)对肠道屏障的联合作用。雄性 ICR 小鼠随机分为 18 组(3 种饲料类型 * 3 暴露长度 * 2 LPS 剂量),并喂食正常或 TiO2 混合饲料(含 1%(质量分数,w/w)TiO2 NPs 或 TiO2 MPs) 1、3、6 个月,然后单次口服 0 或 10 毫克/(公斤体重)LPS。四小时后,评估二氧化钛的运输、肠道屏障功能和炎症反应。暴露 1 个月和 3 个月后,TiO2 均显着增加了肠绒毛高度/隐窝深度比率,并在暴露 1 个月后增加了回肠紧密连接蛋白(ZO-1 和 occludin)的表达。暴露 6 个月后,TiO2 NPs 导致饲料消耗减少,TiO2 MPs 导致小肠中多余的微绒毛和血细胞中 Ti 含量升高。两个 TiO2 暴露组的肠道通透性没有变化。LPS 给药后,我们观察到肠绒毛高度/隐窝深度比率改变,肠道通透性 (DAO) 降低,并且在两个 (TiO2 + LPS) 暴露组中回肠 ZO-1 的表达上调。除了LPS治疗组血清TNF-α水平升高外,回肠或血清细胞因子没有显着变化。在 TiO2 NPs 和 LPS 之间发现了拮抗作用,但 TiO2 MPs 和 LPS 之间存在复杂的相互作用。长期摄入食品添加剂二氧化钛可在不影响肠道屏障功能的情况下改变肠上皮结构。TiO2 和 LPS 的共同暴露会增强肠道屏障功能而不引起显着的炎症反应,并且 TiO2 NPs 和 LPS 之间存在拮抗作用。观察到的所有微小影响都可能与 TiO2 与饲料一起摄入的温和暴露方法有关。
更新日期:2021-02-17
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