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Metabolomic study in plasma, liver and kidney of mice exposed to inorganic arsenic based on mass spectrometry

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Abstract

The mechanism of arsenic toxicity still remains unclear, although enzymatic inhibition, impaired antioxidants metabolism and oxidative stress may play a role. The toxicological effects of trivalent inorganic arsenic on laboratory mouse Mus musculus after oral administration (3 mg/kg body weight/day) were investigated along 12 days, using a metabolomic approach based on direct infusion mass spectrometry to polar and lipophilic extracts from different organs and fluids (liver, kidney, and plasma). Positive and negative acquisition modes (ESI+/ESI−) were used throughout the experiments. The most significant endogenous metabolites affected by exposure were traced by partial least square-discriminant analysis and confirmed by tandem mass spectrometry (MS/MS) and gas chromatography coupled to MS. In this work, the toxic effect of arsenic has been related with important metabolic pathways, such as energy metabolism (e.g., glycolysis, Krebs cycle), amino acids metabolism, choline metabolism, methionine cycle, and degradation of membrane phospholipids (cell apoptosis). In addition, this work illustrates the high reliability of mass spectrometry based on a metabolomic approach to study the biochemical effects induced by metal exposure.

Metabolomic study in plasma, liver and kidney of mice exposed to inorganic arsenic based on mass spectrometry

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Acknowledgments

This work was supported by the project CTM2012-38720-C03-01 from the Spanish Ministry of Economy and Competitiveness, and by projects P08-FQM-3554, P09-FQM-4659, P08-CVI-03829, and P08-RNM-00523 from the Regional Ministry of Economy, Innovation, Science and Employment (Andalusian Government, Spain). M.A. García Sevillano thanks the Spanish Ministry of Education for a PhD scholarship.

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Authors and Affiliations

  1. Department of Chemistry and Materials Science, Faculty of Experimental Science, University of Huelva, Campus de El Carmen, 21007, Huelva, Spain

    M. A. García-Sevillano, M. Contreras-Acuña, T. García-Barrera & J. L. Gómez-Ariza

  2. Research Center on Health and Environment (CYSMA), University of Huelva, Campus El Carmen, 21007, Huelva, Spain

    M. A. García-Sevillano, M. Contreras-Acuña, T. García-Barrera & J. L. Gómez-Ariza

  3. International Campus of Excellence on Agrofood (ceiA3), University of Huelva, Campus El Carmen, 21007, Huelva, Spain

    M. A. García-Sevillano, M. Contreras-Acuña, T. García-Barrera & J. L. Gómez-Ariza

  4. Department of Environmental Biology and Public Health, Cell Biology. Faculty of Experimental Sciences, University of Huelva, Campus El Carmen, 21007, Huelva, Spain

    F. Navarro

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  1. M. A. García-Sevillano
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  2. M. Contreras-Acuña
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  3. T. García-Barrera
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  5. J. L. Gómez-Ariza
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Correspondence to T. García-Barrera or J. L. Gómez-Ariza.

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García-Sevillano, M.A., Contreras-Acuña, M., García-Barrera, T. et al. Metabolomic study in plasma, liver and kidney of mice exposed to inorganic arsenic based on mass spectrometry. Anal Bioanal Chem 406, 1455–1469 (2014). https://doi.org/10.1007/s00216-013-7564-z

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  • DOI: https://doi.org/10.1007/s00216-013-7564-z

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