The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice

被引:46
作者
Nemmar, Abderrahim [1 ]
Al-Salam, Suhail [2 ]
Beegam, Sumaya [1 ]
Yuvaraju, Priya [2 ]
Ali, Badreldin H. [3 ]
机构
[1] United Arab Emirates Univ, Coll Med & Hlth Sci, Dept Physiol, Med Campus,POB 17666, Al Ain, U Arab Emirates
[2] United Arab Emirates Univ, Dept Pathol, Coll Med & Hlth Sci, Al Ain, U Arab Emirates
[3] Sultan Qaboos Univ, Dept Pharmacol & Clin Pharm, Coll Med & Hlth Sci, Muscat, Oman
来源
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2017年 / 12卷
关键词
cerium oxide nanoparticles; coagulation; lung inflammation; oxidative stress; thrombosis; platelet aggregation; bronchoalveolar lavage; DIESEL EXHAUST PARTICLES; OXIDATIVE STRESS; INFLAMMATORY RESPONSES; SMOKING EXPOSURE; TOXICITY; INHALATION; HOMEOSTASIS; INDUCTION; LUNG;
D O I
10.2147/IJN.S127180
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Cerium oxide nanoparticles (CeO2 NPs), used as a diesel fuel catalyst, can be emitted into the ambient air, resulting in exposure to humans by inhalation. Recent studies have reported the development of lung toxicity after pulmonary exposure to CeO2 NPs. However, little is known about the possible thrombotic effects of these NPs. The present study investigated the acute (24 hours) effect of intratracheal (IT) instillation of either CeO2 NPs (0.1 or 0.5 mg/kg) or saline (control) on pulmonary and systemic inflammation and oxidative stress and thrombosis in mice. CeO2 NPs induced a significant increase of neutrophils into the bronchoalveolar lavage (BAL) fluid with an elevation of tumor necrosis factor a (TNF alpha) and a decrease in the activity of the antioxidant catalase. Lung sections of mice exposed to CeO2 NPs showed a dose-dependent infiltration of inflammatory cells consisting of macrophages and neutrophils. Similarly, the plasma levels of C-reactive protein and TNF alpha were significantly increased, whereas the activities of catalase and total antioxidant were significantly decreased. Interestingly, CeO2 NPs significantly and dose dependently induced a shortening of the thrombotic occlusion time in pial arterioles and venules. Moreover, the plasma concentrations of fibrinogen and plasminogen activator inhibitor-1 were significantly elevated by CeO2 NPs. The direct addition of CeO2 NPs (1, 5, or 25 mu g/mL) to mouse whole blood, collected from the inferior vena cava, in vitro neither caused significant platelet aggregation nor affected prothrombin time or partial thromboplastin time, suggesting that the thrombotic events observed in vivo may have resulted from systemic inflammation and/or oxidative stress induced by CeO2 NPs. This study concludes that acute pulmonary exposure to CeO2 NPs induces pulmonary and systemic inflammation and oxidative stress and promotes thrombosis in vivo.
引用
收藏
页码:2913 / 2922
页数:10
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