title: The acute proinflammatory and prothrombotic effects of pulmonary exposure to rutile TiO2 nanorods in rats.
abstract: 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 (TiO2) 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 TiO2 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 TiO2 nanorods; this result indicated the occurrence of platelet aggregation in vivo. The direct addition of TiO2 nanorods (0.4-10 microg/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.
authors: Faculty of Medicine and Health Sciences, Department of Physiology, United Arab Emirates University, PO Box 17666, Al Ain, UAE. anemmar@uaeu.ac.ae
authors: Abderrahim
authors: A
authors: Nemmar
authors: Khaled
authors: K
authors: Melghit
authors: Badreldin H
authors: BH
authors: Ali
mesh_terms: D000208:Acute Disease; D000818:Animals; D001772:Blood Cell Count; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D004489:Edema, Cardiac / Q000139:chemically induced; D008297:Male; D046529:Microscopy, Electron, Transmission; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D010974:Platelet Aggregation / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000139:chemically induced* / Q000473:pathology; D014025:Titanium / Q000737:chemistry* / Q000494:pharmacology*; D014961:X-Ray Diffraction
chemical_list: C009495:titanium dioxide; D014025:Titanium