Intragastric exposure to titanium dioxide nanoparticles induced nephrotoxicity in mice, assessed by physiological and gene expression modifications.
Intragastric exposure to titanium dioxide nanoparticles induced nephrotoxicity in mice, assessed by physiological and gene expression modifications.
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通过生理和基因表达修饰评估，胃内暴露于二氧化钛纳米颗粒会引起小鼠肾毒性
DOI：
10.1186/1743-8977-10-4
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发表时间：
2013-02-13
影响因子：
10
通讯作者：
Tang M
中科院分区：
文献类型：
--
作者：
Gui S;Sang X;Zheng L;Ze Y;Zhao X;Sheng L;Sun Q;Cheng Z;Cheng J;Hu R;Wang L;Hong F;Tang M
大量研究表明，纳米二氧化钛(TiO2NPs)对动物有肾毒性作用。然而，肾毒性的多分子机制尚不清楚。以2.5、5和10 mg/kg的纳米二氧化钛连续灌胃染毒小鼠90d，采用全基因组芯片技术研究纳米二氧化钛的生长、元素分布、肾脏氧化应激和肾脏基因表达谱。结果表明，纳米二氧化钛可导致小鼠肾小球数量减少、细胞凋亡、炎性细胞浸润、肾小管组织坏死或结构紊乱、体重减轻、肾脏指数增加、元素分布失衡、活性氧产生以及肾组织中脂质、蛋白质和DNA的过氧化。此外，基因芯片分析显示，在10 mg/kg二氧化钛纳米颗粒暴露的肾脏中，1246个基因的表达发生了显著变化。在改变的基因中，1006个基因分别与免疫/炎症反应、细胞凋亡、生物过程、氧化应激、离子转运、代谢过程、细胞周期、信号转导、细胞成分、转录、翻译和细胞分化相关。特别是Bcl6、CFI和CFD的表达上调引起免疫/炎症反应，Axud1、Cyp4a12a、Cyp4a12b、Cyp4a14和Cyp2d9的表达显著改变导致严重的氧化应激，而Birc5、CRap2和Tfrc的表达显著抑制导致肾细胞凋亡。Axud1、Bcl6、CF1、CFD、Cyp4a12a、Cyp4a12b、Cyp2d9、Birc5、CRap2和Tfrc可能是纳米二氧化钛暴露所致肾脏毒性的潜在生物标志物。
Numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) induced nephrotoxicity in animals. However, the nephrotoxic multiple molecular mechanisms are not clearly understood. Mice were exposed to 2.5, 5 and 10 mg/kg TiO2 NPs by intragastric administration for 90 consecutive days, and their growth, element distribution, and oxidative stress in kidney as well as kidney gene expression profile were investigated using whole-genome microarray analysis technique. Our findings suggest that TiO2 NPs resulted in significant reduction of renal glomerulus number, apoptosis, infiltration of inflammatory cells, tissue necrosis or disorganization of renal tubules, coupled with decreased body weight, increased kidney indices, unbalance of element distribution, production of reactive oxygen species and peroxidation of lipid, protein and DNA in mouse kidney tissue. Furthermore, microarray analysis showed significant alterations in the expression of 1, 246 genes in the 10 mg/kg TiO2 NPs-exposed kidney. Of the genes altered, 1006 genes were associated with immune/inflammatory responses, apoptosis, biological processes, oxidative stress, ion transport, metabolic processes, the cell cycle, signal transduction, cell component, transcription, translation and cell differentiation, respectively. Specifically, the vital up-regulation of Bcl6, Cfi and Cfd caused immune/ inflammatory responses, the significant alterations of Axud1, Cyp4a12a, Cyp4a12b, Cyp4a14, and Cyp2d9 expression resulted in severe oxidative stress, and great suppression of Birc5, Crap2, and Tfrc expression led to renal cell apoptosis. Axud1, Bcl6, Cf1, Cfd, Cyp4a12a, Cyp4a12b, Cyp2d9, Birc5, Crap2, and Tfrc may be potential biomarkers of kidney toxicity caused by TiO2 NPs exposure.
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影响因子：
10.8
作者：
Burns AA;Vider J;Ow H;Herz E;Penate-Medina O;Baumgart M;Larson SM;Wiesner U;Bradbury M
通讯作者：
Bradbury M
影响因子：
4.4
作者：
Grober OM;Mutarelli M;Giurato G;Ravo M;Cicatiello L;De Filippo MR;Ferraro L;Nassa G;Papa MF;Paris O;Tarallo R;Luo S;Schroth GP;Benes V;Weisz A
通讯作者：
Weisz A
影响因子：
4.5
作者：
Gurr, JR;Wang, ASS;Jan, KY
通讯作者：
Jan, KY
影响因子：
4.9
作者：
Jain, Tapan K.;Reddy, Maram K.;Labhasetwar, Vinod
通讯作者：
Labhasetwar, Vinod
影响因子：
5.1
作者：
Hyndman, D;Bauman, DR;Penning, TM
通讯作者：
Penning, TM