The acute proinflammatory and prothrombotic effects of pulmonary exposure to rutile TiO2 nanorods in rats
The acute proinflammatory and prothrombotic effects of pulmonary exposure to rutile TiO2 nanorods in rats
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DOI：
10.3181/0706-rm-165
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发表时间：
2008-05-01
影响因子：
3.2
通讯作者：
Ali, Badreldin H.
中科院分区：
文献类型：
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作者：
Nemmar, Abderrahim;Melghit, Khaled;Ali, Badreldin H.
纳米技术在工业中得到广泛应用，并广泛探索其在医学中的可能应用。然而，其潜在的呼吸系统和全身不良反应仍然未知。采用软化学方法在室温下制备了具有金红石结构的纯二氧化钛纳米棒。通过粉末X射线衍射证实了TiO 2金红石纳米棒的结构，并通过透射电子显微镜揭示了其尺寸。此后，我们研究了在Wistar大鼠中，这些金红石TiO 2纳米棒（1和5 mg/kg）的气管内滴注对肺部炎症（通过支气管肺泡灌洗评估）、全身炎症和全血中血小板聚集的急性（24小时）影响。与暴露于溶剂的大鼠相比，接受气管内滴注TiO 2纳米棒的大鼠在1（+50%）和5 mg/kg（+81%; P < 0.05）时，其支气管肺泡灌洗液中的巨噬细胞数量呈剂量依赖性增加，中性粒细胞在1（+294%）和5 mg/kg（+4117%; P< 0.01）时流入。两种剂量的金红石型二氧化钛纳米棒引起肺和心脏水肿，通过分析湿重与干重的比值进行评估。同样，血液中的单核细胞和粒细胞的数量在暴露于金红石TiO 2纳米棒后以剂量依赖性方式增加。与此相反，血小板的数量显着减少后，肺暴露于5 mg/kg的二氧化钛纳米棒;这一结果表明，在体内发生血小板聚集。直接添加二氧化钛纳米棒（0.4-10 μ g/ml）到未经处理的大鼠血液显着诱导血小板聚集在体外剂量依赖性的方式。结论是金红石型二氧化钛纳米棒的气管内滴注引起肺部炎症，肺和心脏水肿，全身炎症的上调。金红石型TiO 2纳米棒也在体内和体外引发血小板聚集。
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 dosedependent 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 dosedependent 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 mu g/ml) to untreated rat blood significantly induced platelet aggregation in a dosedependent 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.