Department of Applied Nutritional Toxicology, Institute of Nutritional Sciences, Friedrich Schiller University, Jena, Germany.
Swimming and Bathing Pool Water, Chemical Analytics, German Environment Agency, Bad Elster, Germany.
Part Fibre Toxicol. 2022 May 30;19(1):39. doi: 10.1186/s12989-022-00479-6.
Zinc oxide nanoparticles (ZnO NP) offer beneficial properties for many applications, especially in the food sector. Consequently, as part of the human food chain, they are taken up orally. The toxicological evaluation of orally ingested ZnO NP is still controversial. In addition, their physicochemical properties can change during digestion, which leads to an altered biological behaviour. Therefore, the aim of our study was to investigate the fate of two different sized ZnO NP (< 50 nm and < 100 nm) during in vitro digestion and their effects on model systems of the intestinal barrier. Differentiated Caco-2 cells were used in mono- and coculture with mucus-producing HT29-MTX cells. The cellular uptake, the impact on the monolayer barrier integrity and cytotoxic effects were investigated after 24 h exposure to 123-614 µM ZnO NP.
In vitro digested ZnO NP went through a morphological and chemical transformation with about 70% free zinc ions after the intestinal phase. The cellular zinc content increased dose-dependently up to threefold in the monoculture and fourfold in the coculture after treatment with digested ZnO NP. This led to reactive oxygen species but showed no impact on cellular organelles, the metabolic activity, and the mitochondrial membrane potential. Only very small amounts of zinc (< 0.7%) reached the basolateral area, which is due to the unmodified transepithelial electrical resistance, permeability, and cytoskeletal morphology.
Our results reveal that digested and, therefore, modified ZnO NP interact with cells of an intact intestinal barrier. But this is not associated with serious cell damage.
氧化锌纳米粒子(ZnO NP)具有许多应用的有益特性,尤其是在食品领域。因此,作为人类食物链的一部分,它们通过口服被吸收。口服摄入的 ZnO NP 的毒理学评价仍然存在争议。此外,它们的物理化学性质在消化过程中会发生变化,从而导致生物行为发生改变。因此,我们的研究目的是研究两种不同尺寸的 ZnO NP(<50nm 和 <100nm)在体外消化过程中的命运及其对肠道屏障模型系统的影响。分化的 Caco-2 细胞分别与黏液产生 HT29-MTX 细胞进行单核和共培养。在暴露于 123-614µM ZnO NP 24 小时后,研究了细胞摄取、对单层屏障完整性的影响和细胞毒性作用。
在体外消化过程中,ZnO NP 经历了形态和化学转化,在肠相后有约 70%的游离锌离子。在单核培养物和共培养物中,经消化的 ZnO NP 处理后,细胞内锌含量呈剂量依赖性增加,单核培养物中增加了三倍,共培养物中增加了四倍。这导致了活性氧的产生,但对细胞细胞器、代谢活性和线粒体膜电位没有影响。只有少量的锌(<0.7%)到达基底外侧区域,这是由于未改变的跨上皮电阻、通透性和细胞骨架形态。
我们的结果表明,消化后的 ZnO NP 与完整肠道屏障的细胞相互作用。但这与严重的细胞损伤无关。