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

¹ United Arab Emirates University, Faculty of Medicine and Health Sciences
² Sultan Qaboos University, College of Sciences
³ Sultan Qaboos University, College Medicine and Health Sciences

^* To whom correspondence should be addressed. E-mail: anemmar{at}uaeu.ac.ae.

	Abstract

Nanotechnology is extensively used in industry, and is widely explored for possible applications in medicine. However, their potential respiratory and systemic adverse effects remain unknown. Here, pure titanium dioxide (TiO2) nanorods with rutile structure were prepared at room temperature using soft chemistry technique. TiO2 rutile nanorods structure 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 h) effects of intratracheal (i.t.) instillation of these rutile TiO2 nanorods (1 and 5 mg/kg) on lung inflammation, assessed by bronchoalveolar lavage (BAL), systemic inflammation and platelet aggregation in whole blood. I.t. instillation of TiO2 nanorods induced a dose-dependent increase in macrophage numbers at 1 (+ 50%) and 5 mg/kg (+ 81%, p<0.05) and influx of neutrophils at 1 (+ 294%) and 5 mg/kg (+ 4,117%, p<0.01) in BAL compared to vehicle-exposed rats. Both doses of rutile TiO2 nanorods caused pulmonary and cardiac edema, assessed by the wet-to-dry weight ratio. Similarly, the numbers of monocytes and granulocytes dose-dependently increased in the blood after the exposure to rutile TiO2 nanorods. In contrast, the number of platelets was significantly reduced following pulmonary exposure to 5mg/kg TiO2 nanorods, indicating the occurrence of platelet aggregation in vivo. The direct addition of 0.4-10 µg/ml TiO2 nanorods to untreated rat blood, significantly and dose-dependently induced platelet aggregation in vitro. It is concluded that the i.t. instillation of rutile TiO2 nanorods caused upregulation of lung inflammation, pulmonary and cardiac edema, and systemic inflammation. The rutile TiO2 nanorods also triggered platelet aggregation both in vivo and in vitro.

Key Words: Nanotechnology, Nanoparticulate, Lung, Toxicity