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

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 (TiO2 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 TiO2 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 TiO2 NPs. Lipid and lipid-like metabolites were the most significant classes among the metabolite products induced by TiO2 NPs. TiO2 NPs resulted in a dose-dependent increase in intracellular ROS levels, and correlated with most of the differential metabolites. In conclusion, TiO2 NPs increased the level of the oxidative stress, which could contribute to the altered signature represented by lipid metabolism in BEAS-2B cells.