Serum metabolomic signatures of Sprague-Dawley rats after oral administration of titanium dioxide nanoparticles

Titanium dioxide is widely used as a food additive (E 171), 36% of its composition is nanoparticles. Existing studies have found oral toxic effects of titanium dioxide nanoparticles (TiO2 NPs) on several organs and systems in vivo. Thus, TiO2 NPs may affect the whole body through the internal circulation system. To explore the adverse effect on serum after subchronic exposure to TiO2 NPs, we examined male Sprague-Dawley rats orally administered with TiO2 NPs at a dose of 50 mg/kg body weight per day for 90 days. Serum metabolomics was carried out through high performance liquid chromatography-mass spectrometry (HPLC-MS). Body weight of rats was decreased in the exposure group, which was unrelated with food intake. Through bioinformation analysis, we found different metabolic signatures between the exposure and control groups. There were 17 differential metabolites between the two groups, including 9 amino acids changed and two antioxidants (Propionylcarnitine and kynurenic acid) increased. KEGG pathway analysis revealed that two metabolic pathways significantly altered in the exposure group, including Arginine biosynthesis and Glutathione metabolism, which were both oxidative stress associated. The increased malondialdehyde (MDA), decreased activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were further discovered in serum. In summary, our research suggested that oral exposure to TiO2 NPs could disturb serum metabolism and cause oxidative stress. Interfering with the assimilation and metabolism of amino acid might be the indirect pathway of toxic effects induced by TiO2 NPs.