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Metabolic profiling reveals disorder of carbohydrate metabolism in mouse fibroblast cells induced by titanium dioxide nanoparticles

Authors

  • Chengyu Jin,

    Corresponding author
    1. Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, China
    2. Shanghai 9th People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    • Correspondence to: Chengyu Jin Instrumental Analysis Center, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China.

      E-mail: cyjin@sjtu.edu.cn

      Yumin Liu, School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China.

      E-mail: ymliu@sjtu.edu.cn

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    • These authors contributed equally to this work.
  • Yumin Liu,

    Corresponding author
    1. School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
    • Correspondence to: Chengyu Jin Instrumental Analysis Center, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China.

      E-mail: cyjin@sjtu.edu.cn

      Yumin Liu, School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China.

      E-mail: ymliu@sjtu.edu.cn

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    • These authors contributed equally to this work.
  • Limin Sun,

    1. Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, China
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  • Tianlu Chen,

    1. X-omics Research Centre for Metabolic Diseases, Shanghai 6th People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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  • Yinan Zhang,

    1. X-omics Research Centre for Metabolic Diseases, Shanghai 6th People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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  • Aihua Zhao,

    1. School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
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  • Xiaoyan Wang,

    1. School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
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  • Melanie Cristau,

    1. School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China
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  • Kaisheng Wang,

    1. School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
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  • Wei Jia

    1. School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
    2. Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC, USA
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ABSTRACT

As titanium dioxide (TiO2) nanoparticles are widely used commercially, their potential biosafety and metabolic mechanism needs to be fully explained. In this study, the cytotoxicity of homogeneous and weakly aggregated (< 100 nm) TiO2 nanoparticles was investigated by analyzing the changes in metabolite profiles both in mouse fibroblast (L929) cells and their corresponding culture media using gas chromatograph with a time-of-flight mass spectrometry (GC/TOFMS)-based metabolomic strategy. With multivariate statistics analysis, satisfactory separations were observed in principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models. Based on the variable importance in the OPLS-DA models, a series of differential metabolites were identified by comparison between TiO2 nanoparticle-treated L929 cells or their corresponding culture media and the control groups. It was found that the major biochemical metabolism (carbohydrate metabolism) was suppressed in TiO2 nanoparticle-treated L929 cells and their corresponding culture media. These results might account for the serious damage to energy metabolism in mitochondria and the increased cellular oxidation stress in TiO2 nanoparticle-induced L929 cells. These results also suggest that the metabolomic strategy had a great potential in evaluating the cytotoxicity of TiO2 nanoparticles and thus was very helpful in understanding its underlying molecular mechanisms. Copyright © 2012 John Wiley & Sons, Ltd.

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