Bioactive, oxygenated metabolites of polyunsaturated fatty acids (PUFAs) are important indicators of inflammation and oxidative stress but almost nothing is known about their interactions with nanomaterials (NMs). To investigate the effects of nano-sized materials (n-TiO₂, n-ZnO, n-Ag) and their bulk-sized or ionic (b-TiO₂, b-ZnO, i-Ag) counterpart, we studied the status of oxidative stress and PUFA metabolism in THP-1 cells at low-toxic concentrations (<15% cytotoxicity) 6 h or 24 h after the particle exposures by LC/MS and microarray. N-Ag had a significant and sustained impact on cellular antioxidant defense, seen as incremental synthesis and accumulation of glutathione (GSH) in the cell, and reduction of superoxide dismutase (SOD) activity. The cellular particle doses were largely dependent on exposure duration and particle dissolution, and active transporter mechanisms controlled the concentration of Zn in cytosol. Even at these sub-toxic concentrations, n-Ag was able to induce statistically significant elevation in the 5-HETE: arachidonic acid ratio at 24 h, which suggests association to oxidative stress and induction of pro-inflammatory responses. This was supported by the enhanced gene expression of chemotaxis-related genes. Overall, THP-1 cells internalized all tested particles, but only n-Ag led to low level of oxidative stress through ROS production and antioxidant balance disruption. N-Ag stimulated arachidonic acid oxidation to form 5-HETE which further magnified the inflammatory responses by enhancing the production of mitochondrial superoxide and leukocyte chemokines. Since the sustained n-Ag uptake was detected, the effects may last long and function as a trigger for the low-grade inflammation playing role in the chronic inflammatory diseases.

多不饱和脂肪酸（PUFA）的具有生物活性的含氧代谢产物是炎症和氧化应激的重要指标，但关于它们与纳米材料（NMs）的相互作用几乎一无所知。研究纳米材料（n-TiO ₂，n-ZnO，n-Ag）及其块状或离子型（b-TiO _{2）的影响}（b-ZnO，i-Ag）对应物，我们研究了LC / MS暴露6 h或24 h后低毒性浓度（<15％细胞毒性）的THP-1细胞中氧化应激和PUFA代谢的状态和微阵列。N-Ag对细胞的抗氧化防御具有重大而持续的影响，被视为谷胱甘肽（GSH）在细胞中的合成和积累的增加，以及超氧化物歧化酶（SOD）活性的降低。细胞颗粒剂量主要取决于暴露时间和颗粒溶解度，主动转运蛋白机制可控制细胞溶质中Zn的浓度。即使在这些亚毒性浓度下，n-Ag仍能在24 h引起5-HETE：花生四烯酸比率的统计学显着升高，这表明与氧化应激和促炎反应的诱导相关。趋化性相关基因的基因表达增强支持了这一点。总体而言，THP-1细胞将所有测试颗粒内在化，但是只有n-Ag通过ROS产生和抗氧化剂平衡破坏导致低水平的氧化应激。N-Ag刺激花生四烯酸氧化形成5-HETE，通过增强线粒体超氧化物和白细胞趋化因子的产生进一步放大了炎症反应。由于检测到了持续的n-Ag摄取，其作用可能持续很长时间，并作为引发低度炎症的触发器，在慢性炎症性疾病中发挥作用。N-Ag刺激花生四烯酸氧化形成5-HETE，通过增强线粒体超氧化物和白细胞趋化因子的产生进一步放大了炎症反应。由于检测到了持续的n-Ag摄取，其作用可能持续很长时间，并作为引发低度炎症的触发器，在慢性炎症性疾病中发挥作用。N-Ag刺激花生四烯酸氧化形成5-HETE，通过增强线粒体超氧化物和白细胞趋化因子的产生进一步放大了炎症反应。由于检测到了持续的n-Ag摄取，其作用可能持续很长时间，并作为引发低度炎症的触发器，在慢性炎症性疾病中发挥作用。