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Shotgun metabolomic approach based on mass spectrometry for hepatic mitochondria of mice under arsenic exposure

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Abstract

Mass spectrometry (MS)-based toxicometabolomics requires analytical approaches for obtaining unbiased metabolic profiles. The present work explores the general application of direct infusion MS using a high mass resolution analyzer (a hybrid systems triple quadrupole–time-of-flight) and a complementary gas chromatography–MS analysis to mitochondria extracts from mouse hepatic cells, emphasizing on mitochondria isolation from hepatic cells with a commercial kit, sample treatment after cell lysis, comprehensive metabolomic analysis and pattern recognition from metabolic profiles. Finally, the metabolomic platform was successfully checked on a case-study based on the exposure experiment of mice Mus musculus to inorganic arsenic during 12 days. Endogenous metabolites alterations were recognized by partial least squares-discriminant analysis. Subsequently, metabolites were identified by combining MS/MS analysis and metabolomics databases. This work reports for the first time the effects of As-exposure on hepatic mitochondria metabolic pathways based on MS, and reveals disturbances in Krebs cycle, β-oxidation pathway, amino acids degradation and perturbations in creatine levels. This non-target analysis provides extensive metabolic information from mitochondrial organelle, which could be applied to toxicology, pharmacology and clinical studies.

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Acknowledgments

This work was supported by the projects CTM2012-38720-C03-01 from Ministerio de Economia y Competitividad (Spain), and P012 FQM-0442 and P009-FQM-4659 from Consejería de Innovación, Ciencia y Empresa (Junta de Andalucía-Spain). Miguel Ángel García Sevillano thanks the Ministerio de Educación for a predoctoral 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, T. García-Barrera & J. L. Gómez-Ariza

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

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

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

    M. A. García-Sevillano, 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 & Z. Montero-Lobato

Authors
  1. M. A. García-Sevillano
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  2. T. García-Barrera
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  3. F. Navarro
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  4. Z. Montero-Lobato
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  5. J. L. Gómez-Ariza
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Corresponding authors

Correspondence to T. García-Barrera or J. L. Gómez-Ariza.

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García-Sevillano, M.A., García-Barrera, T., Navarro, F. et al. Shotgun metabolomic approach based on mass spectrometry for hepatic mitochondria of mice under arsenic exposure. Biometals 28, 341–351 (2015). https://doi.org/10.1007/s10534-015-9837-9

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  • DOI: https://doi.org/10.1007/s10534-015-9837-9

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