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

• Published in: Biometals Vol. 28; no. 2; pp. 341 - 351
• Main Authors: García-Sevillano, M. A., García-Barrera, T., Navarro, F., Montero-Lobato, Z., Gómez-Ariza, J. L.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-04-2015; Springer Nature B.V
• Subjects: Amino acids; Animals; Arsenic; Arsenic - toxicity; Biochemistry; Biomedical and Life Sciences; Cell Biology; Exposure; Gas chromatography; Life Sciences; Liver; Mass spectrometry; Medicine/Public Health; Metabolic Networks and Pathways; Metabolism; Metabolites; Metabolome - drug effects; Metabolomics; Mice; Mice, Inbred BALB C; Microbiology; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mus musculus; Pathways; Pattern recognition; Pharmacology; Pharmacology/Toxicology; Plant Physiology; Rodents; Tandem Mass Spectrometry; Toxicology; Mouse mitochondria; Metabolomics; Arsenic; Toxicometabolomics; Mass spectrometry; Non-target analysis
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-015-9837-9

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.
Graphical Abstract