The acute proinflammatory and prothrombotic effects of pulmonary exposure to rutile TiO₂ nanorods in rats

Nanotechnology is extensively used in industry and is widely explored for possible applications in medicine. However, its potential respiratory and systemic adverse effects remain unknown. Here pure titanium dioxide (TiO ₂) nanorods with rutile structure were prepared at room temperature by using a soft chemistry technique. The structure of the TiO₂ rutile nanorods was confirmed by powder X-ray diffraction, and the size was revealed by transmission electron microscopy. Thereafter, we investigated, in Wistar rats, the acute (24-hr) effects of intratracheal instillation of these rutile TiO₂ nanorods (1 and 5 mg/kg) on lung inflammation (assessed by bronchoalveolar lavage), systemic inflammation, and platelet aggregation in whole blood. Compared with vehicle-exposed rats, rats that underwent intratracheal instillation of TiO₂ nanorods experienced a dose-dependent increase in macrophage numbers at 1 (+50%) and 5 mg/kg (+81%; P < 0.05) and an influx of neutrophils at 1 (+294%) and 5 mg/kg (+4117%; P < 0.01) in their bronchoalveolar lavage fluid. Both doses of rutile TiO ₂ nanorods caused pulmonary and cardiac edema, assessed by analysis of the wet weight-to-dry weight ratios. Similarly, the numbers of monocytes and granulocytes in the blood were increased in a dose-dependent manner after exposure to rutile TiO₂ nanorods. In contrast, the number of platelets was significantly reduced after pulmonary exposure to 5 mg/kg TiO ₂ nanorods; this result indicated the occurrence of platelet aggregation in vivo. The direct addition of TiO₂ nanorods (0.4-10 μg/ml) to untreated rat blood significantly induced platelet aggregation in a dose-dependent fashion in vitro. It is concluded that the intratracheal instillation of rutile TiO₂ nanorods caused upregulation of lung inflammation, pulmonary and cardiac edema, and systemic inflammation. Rutile TiO₂ nanorods also triggered platelet aggregation in vivo and in vitro.