title: Toxicological mechanisms of nanosized titanium dioxide-induced spleen injury in mice after repeated peroral application.
abstract: Due to an increase in surface area per particle weight, nanosized titanium dioxide (nano-TiO2) has greatly increased its function as a catalyst and is used for whitening and brightening foods. However, concerns over the safety of nano-TiO2 have been raised. The purpose of this study was to determine whether the protein kinase MAPKs/PI3-K/Akt signaling pathways and transcription factors are activated prior to or concurrent with COX-2 up-regulation in mouse spleen following exposure to 10 mg/kg BW of pure anatase nano-TiO2 by the intragastric route for 15-90 days. The study clearly showed that nano-TiO2 was deposited in the spleen and resulted in reactive oxygen species production, time-dependent splenic inflammation, and necrosis, coupled with a 12.64-64.06% increase in COX-2 and prostaglandin E2 expression, respectively. Furthermore, nano-TiO2 elevated the expressions of ERK, AP-1, CRE, Akt, JNK2, MAPKs, PI3-K, c-Jun, and c-Fos in the spleen by 1.08-6-fold with increased exposure duration, respectively. These findings suggested that nano-TiO2-induced COX-2 expression may be mediated predominantly through the induction of AP-1 and CRE and that AP-1/CRE induction occurred via the MAPKs/PI3-K/Akt signaling pathways in the spleen. Therefore, the findings suggest the need for caution when using nanomaterials as food additives.
authors.affiliation: Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Xuezi
authors.initials: X
authors.lastname: Sang
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Yuguan
authors.initials: Y
authors.lastname: Ze
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Xiao
authors.initials: X
authors.lastname: Ze
authors.forename: Suxin
authors.initials: S
authors.lastname: Gui
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Sun
authors.forename: Huiting
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Sheng
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yu
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D014025:Titanium / Q000378:metabolism / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone