Metabolomic profiling of ZrO₂ nanoparticles in MC3T3-E1 cells

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.