title: Molecular mechanism of titanium dioxide nanoparticles-induced oxidative injury in the brain of mice.
abstract: Numerous studies have demonstrated that the brain is one of the target organs in acute or chronic titanium dioxide (TiO2) nanoparticles (NPs) toxicity, and oxidative stress plays an important role in this process. However, whether brain oxidative injury responds to TiO2 NPs by activating the P38-nuclear factor-E2-related factor-2 (Nrf-2) pathway is not fully understood. The present study aimed to examine activation of the P38-Nrf-2 signaling pathway associated with oxidative stress in the mouse brain induced by intranasal administration of TiO2 NPs for 90 consecutive days. Our findings indicate that TiO2 NPs caused overproliferation of spongiocytes and hemorrhage in the mouse brain. Furthermore, TiO2 NPs significantly activated p38, c-Jun N-terminal kinase, nuclear factor kappa B, Nrf-2 and heme oxygenase-1 expression in the brain, which in turn, led to increased production of reactive oxygen species, as well as lipid, protein and DNA peroxidation. These findings suggest that TiO2 NPs-induced oxidative damage in the mouse brain may occur via the p38-Nrf-2 signaling pathway. Therefore, application of TiO2 NPs in the environment should be performed with caution.
authors: Medical College, Soochow University, Suzhou 215123, People's Republic of China.
authors: Yuguan
authors: Y
authors: Ze
authors: Lei
authors: L
authors: Zheng
authors: Xiaoyang
authors: X
authors: Zhao
authors: Suxin
authors: S
authors: Gui
authors: Xuezi
authors: X
authors: Sang
authors: Junju
authors: J
authors: Su
authors: Ning
authors: N
authors: Guan
authors: Liyuan
authors: L
authors: Zhu
authors: Lei
authors: L
authors: Sheng
authors: Renping
authors: R
authors: Hu
authors: Jie
authors: J
authors: Cheng
authors: Zhe
authors: Z
authors: Cheng
authors: Qingqing
authors: Q
authors: Sun
authors: Ling
authors: L
authors: Wang
authors: Fashui
authors: F
authors: Hong
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014025:Titanium / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium; D051547:Heme Oxygenase-1; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Brain; Macromolecule oxidation; Nrf-2 activation; Reactive oxygen species; Titanium dioxide nanoparticles