期刊
BIOMETALS
卷 28, 期 2, 页码 341-351出版社
SPRINGER
DOI: 10.1007/s10534-015-9837-9
关键词
Metabolomics; Mass spectrometry; Mouse mitochondria; Arsenic; Toxicometabolomics; Non-target analysis
资金
- Ministerio de Economia y Competitividad (Spain) [CTM2012-38720-C03-01]
- Consejeria de Innovacion, Ciencia y Empresa (Junta de Andalucia-Spain) [P012 FQM-0442, P009-FQM-4659]
- Ministerio de Educacion
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, beta-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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