title: A combination of metallomics and metabolomics studies to evaluate the effects of metal interactions in mammals. Application to Mus musculus mice under arsenic/cadmium exposure.
abstract: Arsenic and cadmium are toxic metals of environmental significance with harmful effects on man. To study the toxicological and biochemical effects of arsenic/cadmium in mammals a combined metallomic and metabolomic approach has been developed, complemented with the measurement of biochemical parameters in blood and histopathological evaluation of liver injury in mice Mus musculus under exposure to both xenobiotics. Size-exclusion chromatography (SEC) was combined with affinity chromatography (AF) and ICP-MS detection using species unspecific isotopic dilution analysis (SUID) to characterize the biological effects of As/Cd on selenium containing proteins in the bloodstream of exposed mice. On the other hand, both direct infusion mass spectrometry (DIMS) and gas chromatography-mass spectrometry (GC-MS) provided information about changes in metabolites caused by metals. The results show that As/Cd exposure produces interactions in the distribution of both toxics between organs and plasma of mice and antagonistic interactions with selenium containing proteins in the bloodstream. Interplay with essential metabolic pathways, such as energy metabolism and breakdown of membrane phospholipids were observed, which are more pronounced under As/Cd exposure. In addition, heavy metal and metalloid causes differential liver injury, manifested by steatosis (non-alcoholic fatty liver disease, NAFLD) and infiltration of blood cells into the space of Disse.
  
  
  CONCLUSIONS
  This work presents new contributions in the study of arsenic/cadmium interactions in mice Mus musculus under controlled exposure. With the combination of metallomic and metabolomic approaches the traffic of As and Cd from liver to kidney by means of blood was observed and excretion of As (as arsenic metabolites) or Cd (as MTCd) is inhibited with the simultaneous administration of As/Cd, and these toxic elements have important influence in the levels of seleno-proteins in the plasma. In addition, the metabolomic approach reveals inhibition of different metabolic cycles such as tricarboxylic acid and phospholipid degradation that causes membrane damage and apoptosis that is histopathologically confirmed. This article is part of a Special Issue entitled: Environmental and structural proteomics.
authors.affiliation: Department of Chemistry and Materials Science, Faculty of Experimental Science, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain; International Agrofood Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: García-Sevillano
authors.affiliation: Department of Chemistry and Materials Science, Faculty of Experimental Science, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain; International Agrofood Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain. Electronic address: tamara@dqcm.uhu.es.
authors.forename: Tamara
authors.initials: T
authors.lastname: García-Barrera
authors.affiliation: Department of Environmental Biology and Public Health, Cell Biology, Faculty of Experimental Sciences, University of Huelva, Campus El Carmen, 21007 Huelva, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Navarro-Roldán
authors.affiliation: Department of Environmental Biology and Public Health, Cell Biology, Faculty of Experimental Sciences, University of Huelva, Campus El Carmen, 21007 Huelva, Spain.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Montero-Lobato
authors.affiliation: Department of Chemistry and Materials Science, Faculty of Experimental Science, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain; International Agrofood Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain. Electronic address: ariza@uhu.es.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Ariza
mesh_terms: D000818:Animals; D001151:Arsenic / Q000097:blood*; D020261:Arsenic Poisoning / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D002104:Cadmium / Q000097:blood*; D002105:Cadmium Poisoning / Q000378:metabolism*; D004781:Environmental Exposure / Q000009:adverse effects; D055442:Metabolome / Q000187:drug effects*; D051379:Mice; D020543:Proteome / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D020543:Proteome; D002104:Cadmium; D001151:Arsenic
keywords: Arsenic; Cadmium; Mass spectrometry; Metabolomics; Metallomics; Metals interactions; Mus musculus