Pulmotoxicological effects caused by long-term titanium dioxide nanoparticles exposure in mice.
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.
Medical College of Soochow University, Suzhou 215123, China.
Qingqing
Q
Sun
Danning
D
Tan
Yuguan
Y
Ze
Xuezi
X
Sang
Xiaorun
X
Liu
Suxin
S
Gui
Zhe
Z
Cheng
Jie
J
Cheng
Renping
R
Hu
Guodong
G
Gao
Gan
G
Liu
Min
M
Zhu
Xiaoyang
X
Zhao
Lei
L
Sheng
Ling
L
Wang
Meng
M
Tang
Fashui
F
Hong
D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000493:pharmacokinetics / Q000633:toxicity*
D051546:Cyclooxygenase 2; D019363:Cytochrome P-450 CYP1A1; D016207:Cytokines; D005978:Glutathione; D018840:HSP70 Heat-Shock Proteins; D051547:Heme Oxygenase-1; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014025:Titanium; C454819:Nfkbid protein, mouse; C009495:titanium dioxide; C077623:Ptgs2 protein, mouse