Toxicological Mechanisms of Nanosized Titanium Dioxide-Induced Spleen Injury in Mice after Repeated Peroral Application

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• 作者：Xuezi Sang ; Bing Li ; Yuguan Ze ; Jie Hong ; Xiao Ze ; Suxin Gui ; Qingqing Sun ; Huiting Liu ; Xiaoyang Zhao ; Lei Sheng ; Dong Liu ; Xiaohong Yu ; Ling Wang ; Fashui Hong
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2013
• 出版时间：June 12, 2013
• 年：2013
• 卷：61
• 期：23
• 页码：5590-5599
• 全文大小：746K
• 年卷期：v.61,no.23(June 12, 2013)
• ISSN：1520-5118

文摘

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鈥?0 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鈥?4.06% 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鈥?-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.

Keywords:

nanosized titanium dioxide; spleen damage; cyclooxygenase-2; cyclic adenosine monophosphate-response element; MAPKs/PI3-K/Akt signaling pathways