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

Abderrahim Nemmar,1 Suhail Al-Salam,2 Sumaya Beegam,1 Priya Yuvaraju,2 Badreldin H Ali3 1Department of Physiology, 2Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE; 3Department of Pharmacology and Clinical Pharmacy, College of Medicine...

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Autores principales:	Nemmar A, Al-Salam S, Beegam S, Yuvaraju P, Ali BH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	cerium oxide nanoparticles coagulation lung inflammation oxidative stress thrombosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d87a1f0f1cf24521bc85f49206fba15f
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spelling	oai:doaj.org-article:d87a1f0f1cf24521bc85f49206fba15f2021-12-02T07:48:10ZThe acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice1178-2013https://doaj.org/article/d87a1f0f1cf24521bc85f49206fba15f2017-04-01T00:00:00Zhttps://www.dovepress.com/the-acute-pulmonary-and-thrombotic-effects-of-cerium-oxide-nanoparticl-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Abderrahim Nemmar,1 Suhail Al-Salam,2 Sumaya Beegam,1 Priya Yuvaraju,2 Badreldin H Ali3 1Department of Physiology, 2Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE; 3Department of Pharmacology and Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Al-Khod, Sultanate of Oman 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. Keywords: cerium oxide nanoparticles, coagulation, lung inflammation, oxidative stress, thrombosis, platelet aggregation, bronchoalveolar lavageNemmar AAl-Salam SBeegam SYuvaraju PAli BHDove Medical Pressarticlecerium oxide nanoparticlescoagulationlung inflammationoxidative stressthrombosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2913-2922 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	cerium oxide nanoparticles coagulation lung inflammation oxidative stress thrombosis Medicine (General) R5-920
spellingShingle	cerium oxide nanoparticles coagulation lung inflammation oxidative stress thrombosis Medicine (General) R5-920 Nemmar A Al-Salam S Beegam S Yuvaraju P Ali BH The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice
description	Abderrahim Nemmar,1 Suhail Al-Salam,2 Sumaya Beegam,1 Priya Yuvaraju,2 Badreldin H Ali3 1Department of Physiology, 2Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE; 3Department of Pharmacology and Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Al-Khod, Sultanate of Oman 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. Keywords: cerium oxide nanoparticles, coagulation, lung inflammation, oxidative stress, thrombosis, platelet aggregation, bronchoalveolar lavage
format	article
author	Nemmar A Al-Salam S Beegam S Yuvaraju P Ali BH
author_facet	Nemmar A Al-Salam S Beegam S Yuvaraju P Ali BH
author_sort	Nemmar A
title	The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice
title_short	The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice
title_full	The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice
title_fullStr	The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice
title_full_unstemmed	The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice
title_sort	acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/d87a1f0f1cf24521bc85f49206fba15f
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The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice

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