title: Oxidative damage of lung and its protective mechanism in mice caused by long-term exposure to titanium dioxide nanoparticles.
abstract: 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.
authors.affiliation: Medical College of Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Sun
authors.forename: Danlin
authors.initials: D
authors.lastname: Tan
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xiaorun
authors.initials: X
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cheng
authors.forename: Gan
authors.initials: G
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Xuezi
authors.initials: X
authors.lastname: Sang
authors.forename: Suxin
authors.initials: S
authors.lastname: Gui
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Renping
authors.initials: R
authors.lastname: Hu
authors.forename: Meng
authors.initials: M
authors.lastname: Tang
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014025:Titanium / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D008315:Malondialdehyde; D014025:Titanium; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase