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Hemopexin as biomarkers for analyzing the biological responses associated with exposure to silica nanoparticles

Kazuma Higashisaka1, Yasuo Yoshioka1*, Kohei Yamashita1, Yuki Morishita1, Huiyan Pan1, Toshinobu Ogura1, Takashi Nagano1, Akiyoshi Kunieda1, Kazuya Nagano2, Yasuhiro Abe3, Haruhiko Kamada24, Shin-ichi Tsunoda24, Hiromi Nabeshi5, Tomoaki Yoshikawa1 and Yasuo Tsutsumi124*

Author Affiliations

1 Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan

2 Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan

3 Cancer Biology Research Center, Sanford Research/USD, 2301 E. 60th Street N, Sioux Falls, SD, 57104, USA

4 The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6, Yamadaoka, Suita, Osaka, 565-0871, Japan

5 Division of Foods, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan

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Nanoscale Research Letters 2012, 7:555  doi:10.1186/1556-276X-7-555

Published: 8 October 2012


Practical uses of nanomaterials are rapidly spreading to a wide variety of fields. However, potential harmful effects of nanomaterials are raising concerns about their safety. Therefore, it is important that a risk assessment system is developed so that the safety of nanomaterials can be evaluated or predicted. Here, we attempted to identify novel biomarkers of nanomaterial-induced health effects by a comprehensive screen of plasma proteins using two-dimensional differential in gel electrophoresis (2D-DIGE) analysis. Initially, we used 2D-DIGE to analyze changes in the level of plasma proteins in mice after intravenous injection via tail veins of 0.8 mg/mouse silica nanoparticles with diameters of 70 nm (nSP70) or saline as controls. By quantitative image analysis, protein spots representing >2.0-fold alteration in expression were found and identified by mass spectrometry. Among these proteins, we focused on hemopexin as a potential biomarker. The levels of hemopexin in the plasma increased as the silica particle size decreased. In addition, the production of hemopexin depended on the characteristics of the nanomaterials. These results suggested that hemopexin could be an additional biomarker for analyzing the biological responses associated with exposure to silica nanoparticles. We believe that this study will contribute to the development of biomarkers to ensure the safety of silica nanoparticles.

Silica nanoparticle; Plasma proteins; Hemolysis; Biomarker