Metabolomic study in plasma, liver and kidney of mice exposed to inorganic arsenic based on mass spectrometry.
The mechanism of arsenic toxicity still remains unclear, although enzymatic inhibition, impaired antioxidants metabolism and oxidative stress may play a role. The toxicological effects of trivalent inorganic arsenic on laboratory mouse Mus musculus after oral administration (3 mg/kg body weight/day) were investigated along 12 days, using a metabolomic approach based on direct infusion mass spectrometry to polar and lipophilic extracts from different organs and fluids (liver, kidney, and plasma). Positive and negative acquisition modes (ESI(+)/ESI(-)) were used throughout the experiments. The most significant endogenous metabolites affected by exposure were traced by partial least square-discriminant analysis and confirmed by tandem mass spectrometry (MS/MS) and gas chromatography coupled to MS. In this work, the toxic effect of arsenic has been related with important metabolic pathways, such as energy metabolism (e.g., glycolysis, Krebs cycle), amino acids metabolism, choline metabolism, methionine cycle, and degradation of membrane phospholipids (cell apoptosis). In addition, this work illustrates the high reliability of mass spectrometry based on a metabolomic approach to study the biochemical effects induced by metal exposure.
Department of Chemistry and Materials Science, Faculty of Experimental Science, University of Huelva, Campus de El Carmen, 21007, Huelva, Spain.
M A
MA
García-Sevillano
M
M
Contreras-Acuña
T
T
García-Barrera
F
F
Navarro
J L
JL
Gómez-Ariza
D000284:Administration, Oral; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000097:blood* / Q000493:pharmacokinetics; D002794:Choline / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D055432:Metabolomics; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010087:Oxides / Q000097:blood* / Q000493:pharmacokinetics / Q000633:toxicity; D010743:Phospholipids / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000596:Amino Acids; D001152:Arsenicals; D010087:Oxides; D010743:Phospholipids; D008715:Methionine; D002794:Choline; D000077237:Arsenic Trioxide