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二氧化钛纳米颗粒诱导人正常支气管上皮(BEAS-2B)细胞代谢组学特征中活性氧(ROS)相关变化。

Titanium dioxide nanoparticles induced reactive oxygen species (ROS) related changes of metabolomics signatures in human normal bronchial epithelial (BEAS-2B) cells.

机构信息

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, PR China.

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, PR China.

出版信息

Toxicol Appl Pharmacol. 2022 Jun 1;444:116020. doi: 10.1016/j.taap.2022.116020. Epub 2022 Apr 14.

DOI:10.1016/j.taap.2022.116020
PMID:35430233
Abstract

Titanium dioxide often enters the respiratory tract in the form of nano-dust in occupational sites. Metabolomics may be a promising method for studying the toxicology of nano titanium dioxide. The intention of this study was to explore the possible impact of titanium dioxide nanoparticles (TiO NPs) on the metabolomics signatures of human normal bronchial epithelial (BEAS-2B) cells and to search for investigate the role of reactive oxygen species (ROS). In this study, BEAS-2B cells were treated by TiO NPs (0, 25, 50 and 100 μg/mL) for 48 h. The metabolites extracted from BEAS-2B cells were determined by untargeted metabolomics technique, and the differential metabolites and metabolic pathways were discovered by using multivariate analysis. Intracellular ROS was detected by DCFH-DA probe and flow cytometry method. Machine learning was used to explore the relationship between ROS and metabolomics changes. Totally, seventy-six differential metabolites and the steroid biosynthesis pathway of BEAS-2B cells were observed after treatment of TiO NPs. Lipid and lipid-like metabolites were the most significant classes among the metabolite products induced by TiO NPs. TiO NPs resulted in a dose-dependent increase in intracellular ROS levels, and correlated with most of the differential metabolites. In conclusion, TiO NPs increased the level of the oxidative stress, which could contribute to the altered signature represented by lipid metabolism in BEAS-2B cells.

摘要

二氧化钛在工作场所常以纳米粉尘的形式进入呼吸道。代谢组学可能是研究纳米二氧化钛毒理学的一种很有前途的方法。本研究旨在探讨二氧化钛纳米颗粒(TiO NPs)对人正常支气管上皮(BEAS-2B)细胞代谢组学特征的可能影响,并寻找活性氧(ROS)的作用。在这项研究中,用 TiO NPs(0、25、50 和 100μg/mL)处理 BEAS-2B 细胞 48 小时。通过非靶向代谢组学技术测定 BEAS-2B 细胞中提取的代谢物,并通过多元分析发现差异代谢物和代谢途径。用 DCFH-DA 探针和流式细胞术检测细胞内 ROS。采用机器学习方法探讨 ROS 与代谢组学变化的关系。经 TiO NPs 处理后,共观察到 76 种差异代谢物和 BEAS-2B 细胞的甾体生物合成途径。脂质和类脂代谢物是 TiO NPs 诱导的代谢产物中最显著的类别。TiO NPs 导致细胞内 ROS 水平呈剂量依赖性增加,并与大多数差异代谢物相关。总之,TiO NPs 增加了氧化应激水平,这可能导致 BEAS-2B 细胞中脂质代谢改变的特征。

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