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Oxidative damage of lung and its protective mechanism in mice caused by long‐term exposure to titanium dioxide nanoparticles
Author(s) -
Sun Qingqing,
Tan Danlin,
Zhou Qiuping,
Liu Xiaorun,
Cheng Zhe,
Liu Gan,
Zhu Min,
Sang Xuezi,
Gui Suxin,
Cheng Jie,
Hu Renping,
Tang Meng,
Hong Fashui
Publication year - 2012
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.34190
Subject(s) - gclc , oxidative stress , gclm , reactive oxygen species , pharmacology , materials science , apoptosis , acetylcysteine , heme oxygenase , lung , heme , biophysics , toxicology , chemistry , biochemistry , biology , medicine , glutathione , antioxidant , enzyme
Exposure to titanium dioxide nanoparticles (TiO 2 NPs) elicits an adverse response such as oxidative damage. The molecular targets of TiO 2 NPs remain largely unidentified. In the present study, the function and signal pathway of nuclear factor erythroid 2 related factor 2 (Nrf2) in protection against TiO 2 NPs‐induced oxidative stress in the mouse lung were investigated. Mice were exposed to 10 mg/kg body weight by an intratracheal administration for 15–90 days. With increasing exposed terms, TiO 2 NPs were significantly accumulated and increased the reactive oxygen species (ROS) production in lung, which resulted in severe pulmonary edema, inflammatory response and pneumonocyte apoptosis for 90 days. Furthermore, TiO 2 NPs exposure could greatly induce expression of Nrf2, heme oxygenase 1 (HO‐1), and glutamate‐cysteine ligase catalytic subunit (GCLC) from 15‐day to 75‐day exposure, whereas 90‐day exposure caused significant decreases of three factors expression levels in lung. Our findings imply that the induction of Nrf2 expression is an adaptive intracellular response to TiO 2 NPs‐induced oxidative stress in the mouse lung, and that Nrf2 is protective against TiO 2 NPs‐induced pulmonary damages during certain exposure terms. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2554–2562, 2012.