title: Shotgun metabolomic approach based on mass spectrometry for hepatic mitochondria of mice under arsenic exposure.
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.
authors.affiliation: Department of Chemistry and Materials Science, Faculty of Experimental Science, University of Huelva, Campus de El Carmen, 21007, Huelva, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: García-Sevillano
authors.forename: T
authors.initials: T
authors.lastname: García-Barrera
authors.forename: F
authors.initials: F
authors.lastname: Navarro
authors.forename: Z
authors.initials: Z
authors.lastname: Montero-Lobato
authors.forename: J L
authors.initials: JL
authors.lastname: Gómez-Ariza
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D053858:Metabolic Networks and Pathways; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D001151:Arsenic