Open Access Research

Intragastric exposure to titanium dioxide nanoparticles induced nephrotoxicity in mice, assessed by physiological and gene expression modifications

Suxin Gui1, Xuezi Sang1, Lei Zheng1, Yuguan Ze1, Xiaoyang Zhao1, Lei Sheng1, Qingqing Sun1, Zhe Cheng1, Jie Cheng1, Renping Hu1, Ling Wang1, Fashui Hong1 and Meng Tang23*

  • * Corresponding author: Meng Tang tm@seu.edu.cn

  • † Equal contributors

Author Affiliations

1 Medical College of Soochow University, Suzhou, 215123, China

2 Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China

3 Jiangsu key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, 210009, China

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Particle and Fibre Toxicology 2013, 10:4  doi:10.1186/1743-8977-10-4

Published: 13 February 2013

Abstract

Background

Numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) induced nephrotoxicity in animals. However, the nephrotoxic multiple molecular mechanisms are not clearly understood.

Methods

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.

Results

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.

Conclusions

Axud1, Bcl6, Cf1, Cfd, Cyp4a12a, Cyp4a12b, Cyp2d9, Birc5, Crap2, and Tfrc may be potential biomarkers of kidney toxicity caused by TiO2 NPs exposure.

Keywords:
Titanium dioxide nanoparticles; Nephrotoxicity; Oxidative stress; Gene-expressed profile; Mice