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

Abderrahim Nemmar*, Suhail Al-Salam, Sumaya Beegam, Priya Yuvaraju, Badreldin H. Ali

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2913-2922
Number of pages10
JournalInternational Journal of Nanomedicine
Volume12
DOIs
Publication statusPublished - Apr 10 2017

Keywords

  • Bronchoalveolar lavage
  • Cerium oxide nanoparticles
  • Coagulation
  • Lung inflammation
  • Oxidative stress
  • Platelet aggregation
  • Thrombosis

ASJC Scopus subject areas

  • Bioengineering
  • Biophysics
  • Biomaterials
  • Drug Discovery
  • Organic Chemistry

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