Abstract
The authors' previous study showed that zirconium oxide nanoparticles (ZrO2 NPs) induce toxic effects in MC3T3-E1 cells; however, its toxicological mechanism is still unclear. Liquid chromatography-mass spectrometry/time-of-flight mass spectrometry was used to reveal the metabolite profile and toxicological mechanism of MC3T3-E1 cells in response to ZrO2 NPs. The results demonstrated that MC3T3-E1 cells treated with ZrO2 NPs for 24 and 48 h presented different metabolic characteristics. Following ZrO2 NP treatment for 24 h, 96 upregulated and 129 downregulated metabolites in the positive ion mode, as well as 91 upregulated and 326 downregulated metabolites in the negative ion mode were identified. Following ZrO2 NP treatment for 48 h, 33 upregulated and 174 downregulated metabolites were identified in the positive ion mode, whereas 37 upregulated and 302 downregulated metabolites were confirmed in the negative ion mode. Among them, 42 differential metabolites were recognised as potential metabolites contributing to the induced toxic effects of ZrO2 NPs in MC3T3-E1 cells. Most of the differential metabolites were lysophosphatidylcholine and lysophosphatidylethanolamide, indicating that exposure to ZrO2 NPs may have a profound impact on human cellular function by impairing the membrane system. The results also provide new clues for the toxicological mechanism of ZrO2 NP dental materials.