Alteration of metabolomic profiles by titanium dioxide nanoparticles in human gingivitis model

Although nanoparticles (NPs) has afforded considerable benefits in various fields of sciences, several reports have shown their harmful effects, suggesting the necessity of adequate risk assessment. To clarify the mechanism of titanium dioxide nanoparticles (TiO₂ NPs)-enhanced gingival inflammation, we conducted the full-scale metabolomic analyses of human gingival fibroblast cells treated with IL-1β alone or in combination with TiO₂ NPs. Observation with transmission electron microscope demonstrated the incorporation of TiO₂ NPs into vacuoles of the cells. TiO₂ NPs significantly enhanced the IL-1β-induced prostaglandin E₂ production and COX-1 and COX-2 protein expression. IL-1β reduced the intracellular concentrations of overall primary metabolites especially those of amino acid, urea cycle, polyamine, S-adenosylmethione and glutathione synthetic pathways. The addition of TiO₂ NPs further augmented these IL-1β-induced metabolic changes, recommending careful use of dental materials containing TiO₂ NPs towards patients with gingivitis or periodontitis. The impact of the present study is to identify the molecular targets of TiO₂ NPs for the future establishment of new metabolic markers and therapeutic strategy of gingival inflammation.