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

Content Provider	Europe PMC
Author	Nemmar, Abderrahim Al-Salam, Suhail Beegam, Sumaya Yuvaraju, Priya Ali, Badreldin H
Copyright Year	2017
Abstract	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 α (TNFα) 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 TNFα 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 μg/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.
ISSN	11769114
Journal	International Journal of Nanomedicine
Volume Number	12
PubMed Central reference number	PMC5391826
PubMed reference number	28435267
e-ISSN	11782013
DOI	10.2147/ijn.s127180
Language	English
Publisher	Dove Medical Press
Publisher Date	2017-04-10
Access Restriction	Open
Rights License	The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. © 2017 Nemmar et al. This work is published and licensed by Dove Medical Press Limited
Subject Keyword	cerium oxide nanoparticles coagulation lung inflammation oxidative stress thrombosis platelet aggregation bronchoalveolar lavage
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Organic Chemistry Drug Discovery Medicine Biomaterials Biophysics Bioengineering Pharmaceutical Science