Metabolomic analysis on the toxicological effects of TiO₂ nanoparticles in mouse fibroblast cells: from the perspective of perturbations in amino acid metabolism.

Titanium dioxide nanoparticles (nano-TiO2) have been widely applied in daily life and subsequent problem on the potential health risk are raised. Studies on the toxicity of nano-TiO2 have shown that they could lead to toxic effects on human and environment. However, the mechanisms are still unclear. We investigated the change of amino acid levels in L929 cells after nano-TiO2 exposure using gas chromatography with time-of-flight mass spectrometry (GC/TOFMS)-based metabolomics approach. Spectral profiles were subjected to multivariate statistics, namely, Principal Component Analysis (PCA), and Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA). Using MetaboAnalyst 2.0, it was found that 7 metabolic pathways (impact-value >0.10) among the regulated pathways were significantly perturbed. Twelve distinct amino acids are identified from these pathways, including L-α-alanine, β-alanine, glycine, L-aspartate, L-methionine, L-cysteine, glutamate, L-pyroglutamate, L-asparagine, L-glutamine, S-adenosylmethionine, and L-lysine. These results show that the disturbed amino acids played an important role in the nano-TiO2-induced cytotoxicity. Along with earlier findings, we successfully used the metabolomics approaches to manifest nano-TiO2 toxicity through triggering cellular oxidative stress, energy damage and the inhibition of DNA and RNA synthesis.