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Pulmotoxicological effects caused by long-term titanium dioxide nanoparticles exposure in mice.

Abstract
Exposure to titanium dioxide nanoparticles (TiO(2) NPs) has been demonstrated to result in pulmonary inflammation in animals; however, very little is known about the molecular mechanisms of pulmonary injury due to TiO(2) NPs exposure. The aim of this study was to evaluate the oxidative stress and molecular mechanism associated with pulmonary inflammation in chronic lung toxicity caused by the intratracheal instillation of TiO(2) NPs for 90 consecutive days in mice. Our findings suggest that TiO(2) NPs are significantly accumulated in the lung, leading to an obvious increase in lung indices, inflammation and bleeding in the lung. Exposure to TiO(2) NPs significantly increased the accumulation of reactive oxygen species and the level of lipid peroxidation, and decreased antioxidant capacity in the lung. Furthermore, TiO(2) NPs exposure activated nuclear factor-κB, increased the levels of tumor necrosis factor-α, cyclooxygenase-2, heme oxygenase-1, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1β, and CYP1A1 expression. However, TiO(2) NPs exposure decreased NF-κB-inhibiting factor and heat shock protein 70 expression. Our results suggest that the generation of pulmonary inflammation caused by TiO(2) NPs in mice is closely related to oxidative stress and the expression of inflammatory cytokines.
AuthorsQingqing Sun, Danning Tan, Yuguan Ze, Xuezi Sang, Xiaorun Liu, Suxin Gui, Zhe Cheng, Jie Cheng, Renping Hu, Guodong Gao, Gan Liu, Min Zhu, Xiaoyang Zhao, Lei Sheng, Ling Wang, Meng Tang, Fashui Hong
JournalJournal of hazardous materials (J Hazard Mater) Vol. 235-236 Pg. 47-53 (Oct 15 2012) ISSN: 1873-3336 [Electronic] Netherlands
PMID22898172 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Cytokines
  • HSP70 Heat-Shock Proteins
  • IkappaBNS protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Proteins
  • RNA, Messenger
  • Reactive Oxygen Species
  • titanium dioxide
  • Titanium
  • Cytochrome P-450 CYP1A1
  • Heme Oxygenase-1
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Glutathione
Topics
  • Animals
  • Cyclooxygenase 2 (genetics, metabolism)
  • Cytochrome P-450 CYP1A1 (genetics, metabolism)
  • Cytokines (genetics, metabolism)
  • Glutathione (metabolism)
  • HSP70 Heat-Shock Proteins (genetics, metabolism)
  • Heme Oxygenase-1 (genetics, metabolism)
  • Intracellular Signaling Peptides and Proteins
  • Lipid Peroxidation (drug effects)
  • Lung (drug effects, metabolism, pathology)
  • Male
  • Metal Nanoparticles (toxicity)
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B (genetics, metabolism)
  • Nanoparticles (toxicity)
  • Oxidative Stress (drug effects)
  • Proteins (genetics, metabolism)
  • RNA, Messenger (metabolism)
  • Reactive Oxygen Species (metabolism)
  • Titanium (pharmacokinetics, toxicity)

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