Titanium dioxide nanoparticles Disrupt ultrastructure and function of Rat thyroid tissue via oxidative stress

Nano-TiO₂ is widely used in various fields such as industry, daily necessities, food and medicine. Previous studies have shown that it can enter mammalian tissues through the digestive tract or respiratory tract and have effects on various organs and systems. However, the effect of nano-TiO₂ on the mammalian thyroid gland has not been reported. In this study, we fed SD rats with rutile nano-TiO₂ at a dose of 5 mg/kg body weight for 3 weeks, and then examined the thyroid histology and thyroid function of the rats. In vitro experiments were conducted to determine the effects of nano-TiO₂ on the viability, apoptosis, inflammatory factors, antioxidant enzymes, and oxidative stress of human thyroid follicular epithelial cells. Histological evidence showed abnormal morphology of rat thyroid follicles and organelle damage in follicular epithelial cells. Nano-TiO₂ caused a decrease in the level of sodium/iodide symporter (NIS), an increase in the level of apoptotic protein cleaved-caspase 3, and an increase in the levels of pro-inflammatory factors IL-1β and TNF-α in rat thyroid tissue. Nano-TiO₂ also resulted in increased serum FT4 and TPO-Ab levels. In in vitro experiments, nano-TiO₂ reduced the viability of human thyroid follicular cells, downregulated the levels and activities of antioxidant enzymes CAT, GPX1 and SOD, and increased the levels of ROS and MDA caused by oxidative stress. These results indicate that nano-TiO₂ damages the structure and function of thyroid follicular epithelial cells through oxidative stress. Long-term exposure to nano-TiO₂ could be a potential risk factor for thyroid dysfunction.