Shotgun metabolomic approach based on mass spectro

Authors: M A GarcíaSevillano T GarcíaBarrera F Navarro Z MonteroLobato J L GómezAriza

Publish Date: 2015/03/10

Volume: 28, Issue: 2, Pages: 341-351

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Abstract

Mass spectrometry MSbased 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–timeofflight 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 casestudy based on the exposure experiment of mice Mus musculus to inorganic arsenic during 12 days Endogenous metabolites alterations were recognized by partial least squaresdiscriminant analysis Subsequently metabolites were identified by combining MS/MS analysis and metabolomics databases This work reports for the first time the effects of Asexposure on hepatic mitochondria metabolic pathways based on MS and reveals disturbances in Krebs cycle βoxidation pathway amino acids degradation and perturbations in creatine levels This nontarget analysis provides extensive metabolic information from mitochondrial organelle which could be applied to toxicology pharmacology and clinical studiesThis work was supported by the projects CTM201238720C0301 from Ministerio de Economia y Competitividad Spain and P012 FQM0442 and P009FQM4659 from Consejería de Innovación Ciencia y Empresa Junta de AndalucíaSpain Miguel Ángel García Sevillano thanks the Ministerio de Educación for a predoctoral scholarship

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