Oral exposure of titanium oxide nanoparticles induce ileum physical barrier dysfunction via Th1/Th2 imbalance

In this work, we aimed to evaluate the adverse effects and the mechanism of intestinal barrier caused by titanium dioxide nanoparticles (TiO₂ NPs). Here, the effects of two different dosages (300 and 1200 mg/kg) of TiO₂ NPs on female mice (n = 5) were investigated. After 28-day oral exposure, the results of Ti content were significantly increased in the ileum in comparison with the control. The histopathological structure index of the ileum was significantly changed after TiO₂ NPs exposure; villi height and crypt depth were decreased and increased, respectively. Meanwhile, TiO₂ NPs treatment also significantly altered the transcription levels of genes. First, the GATA-3 and STAT-4 were upregulation and downregulation, respectively. Second, gene expressions of the Zonula Occludens-1, claudin (CLDN)-12, occludin, and myosin light chain kinase were significantly upregulated, while the CLDN-3 was decreased. Finally, the caspase-3, caspase-9, and caspase-12 were upregulated. The results of TUNEL staining indicated apoptosis in the ileum. In general, TiO₂ NPs treatment significantly changed the intestine physical barrier in a dose-dependent manner. The toxicity of TiO₂ NPs could be through the imbalance in the Th1/Th2.