Metallomics pp 39-66 | Cite as

Environmental Metallomics

  • Gema Rodríguez-Moro
  • Sara Ramírez-Acosta
  • Ana Arias-Borrego
  • Tamara García-Barrera
  • José Luis Gómez-ArizaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1055)


Metallomics is the new paradigm about the metallobiomolecules related to living organisms, considering the interactions between toxic and essential metals, transport through biological fluids, passing across biological membranes and interfaces, synergic and antagonist actions among metal species, and alterations in metabolic pathways triggered by overexpression or inhibition of these metallobiomolecules. These challenging studies require the development of new analytical approaches in order to get suitable information of these species close to their native environment which has promoted the application of new tools based in mass spectrometry under the double focus of elemental (ICP-MS) and molecular (Qq-TOF-MS) mass spectrometry, generally arranged with chromatography in multidimensional platforms. The driving force for the design of these new analytical instrumental arrangements is the analyst imagination who adapts the new metallomic methodology to the new problems. In this work the most recent metallomic approaches proposed have been considered, deepening their application to the most frequent problems related to metal toxicity in environmental issues, such as exposure experiments of mice to toxic metals, interactions and homeostasis of metals, metal imaging, metabolic alterations caused by metallobiomolecules over- or down-expressed, and more interestingly real-life consequences of metal species expression in environmental field studies. In this way, the application of two-dimensional chromatographic approaches with ICP-MS detection, the use of multidimensional chromatography-column-switching-ICP-MS devices, metal imaging with LA-ICP-MS, combined application of metallomics and metabolomics for environmental toxicological appraisal, and the application of these metallomic techniques in environmental field studies have been reviewed.


Environmental metallomics Two-dimensional chromatographic metallomics Column-switching metallomics Metal exposure Laser ablation, Metabolomics 





Anion exchange chromatography


Anion exchange solid-phase extraction


Affinity chromatography




Bovine serum albumin


Collision/reaction cell


Column-switching valves


Direct infusion mass spectrometry


Dimethylmonothioarsinic acid




Doñana National Park


Glutathione peroxidase


Electrospray ionization




High-performance liquid chromatography


Ion chromatography coupled with inductively coupled plasma mass spectrometry


Inductively coupled plasma mass spectrometry


Isotope dilution analysis


Isoelectric focusing


Laser ablation inductively coupled plasma mass spectrometry


Matrix-assisted laser desorption/ionization mass spectrometry






Nano-electrospray ionization-triple quadrupole-time-of-flight-mass spectrometry




Triple quadrupole-time-of-flight-mass spectrometry


Red blood cells


Reactive oxygen species


Reversed-phase HPLC






Size exclusion chromatography


Selenoprotein P


Superoxide dismutase


Species-unspecific isotope dilution


Tricarboxylic acid cycle




Trimethyl-arsine oxide



This work was supported by the projects CTM2015-67902-C2-1-P and CTM2012-38720-C03-03 from the Spanish Ministry of Economy and Competitiveness and P12-FQM- 0442 from the Regional Ministry of Economy, Innovation, Science and Employment (Andalusian, Government, Spain). Gema Rodríguez Moro and Sara Ramírez Acosta thank the Ministry of Economy and Competitiveness for PhD scholarships BES-2013-064501 and BES-2016-076354, respectively. Finally, the authors are grateful to FEDER (European Community) for the financial support, grant number UNHU13-1E-1611 and UNHU15-CE-3140.


  1. Åkesson A, Bjellerup P, Lundh T, Lidfeldt J, Nerbrand C, Samsioe G, Skerfving S, Marie Vahter M (2006) Cadmium-induced effects on bone in a population-based study of women. Environ Health Perspect 114:830–834PubMedPubMedCentralCrossRefGoogle Scholar
  2. Åkesson A, Julin B, Wolk A (2008) Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence: a population-based prospective cohort study. Cancer Res 68:6435–6441PubMedCrossRefPubMedCentralGoogle Scholar
  3. Åkesson A, Lundh T, Vahter M, Bjellerup P, Lidfeldt J, Nerbrand C, Samsioe G, Strömberg U, Skerfving S (2005) Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure. Environ Health Perspect 113:1627–1631PubMedPubMedCentralCrossRefGoogle Scholar
  4. Almar M, Villa JG, Cuevas MJ, Rodríguez-Marroyo JA, Avila C, González-Gallego J (2002) Urinary levels of 8-hydroxydeoxyguanosine as a marker of oxidative damage in road cycling. Free Radic Res 36:247–253PubMedCrossRefPubMedCentralGoogle Scholar
  5. Ames BN (1989) Endogenous oxidative DNA damage, aging, and cancer. Free Radic Res 7:121–128Google Scholar
  6. Bako G, Smith ES, Hanson J, Dewar R (1982) The geographical distribution of high cadmium concentrations in the environment and prostate cancer in Alberta. Can J Public Health 73:92–94PubMedPubMedCentralGoogle Scholar
  7. Bashir S, Sharma Y, Irshad M, Gupta S, Dogra TD (2006) Arsenic-induced cell death in liver and brain of experimental rats. Basic Clin Pharmacol Toxicol 98:38–43PubMedCrossRefPubMedCentralGoogle Scholar
  8. Becker JS (2010) Bioimaging of metals in brain tissue from micrometre to nanometre scale by laser ablation inductively coupled plasma mass spectrometry: state of the art and perspectives. Int J Mass Spectrom 289:65–75CrossRefGoogle Scholar
  9. Becker JS, Mounicou S, Zoriy MV, Becker JS, Lobinski R (2008) Analysis of metal-binding proteins separated by non-denaturating gel electrophoresis using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Talanta 76:1183–1188PubMedCrossRefPubMedCentralGoogle Scholar
  10. Becker JS, Lobinski R, Sabine Becker J (2009) Metal imaging in non-denaturating 2D electrophoresis gels by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for the detection of metalloproteins. Metallomics 1:312–316PubMedCrossRefPubMedCentralGoogle Scholar
  11. Becker JS, Pozebon D, Matusch A, Dressler VL, Becker JS (2011) Detection of Zn-containing proteins in slug (genus Arion) tissue using laser ablation ICP-MS after separation by gel electrophoresis. Int J Mass Spectrom 307:66–69CrossRefGoogle Scholar
  12. Bogdan GM, Sampayo-Reyes A, Vasken Aposhian H (1994) Arsenic binding proteins of mammalian systems: I. Isolation of three arsenite-binding proteins of rabbit liver. Toxicology 93:175–193PubMedCrossRefPubMedCentralGoogle Scholar
  13. Bonilla-Valverde D, Ruiz-Laguna J, Muñoz A, Ballesteros J, Lorenzo F, Gómez-Ariza JL, López-Barea J (2004) Evolution of biological effects of Aznalcóllar mining spill in the Algerian mouse (Mus spretus) using biochemical biomarkers. Toxicology 197:123–138PubMedCrossRefPubMedCentralGoogle Scholar
  14. Brown KG, Boyle KE, Chen CW, Gibb HJ (1989) A dose-response analysis of skin Cancer from inorganic arsenic in drinking water. Risk Anal 9:519–528PubMedCrossRefPubMedCentralGoogle Scholar
  15. Bucher G, Mounicou S, Simon O, Floriani M, Lobinski R, Frelon S (2016) Insights into the nature of uranium target proteins within zebrafish gills after chronic and acute waterborne exposures. Environ Toxicol Chem 35:736–741PubMedCrossRefPubMedCentralGoogle Scholar
  16. Bucher G, Mounicou S, Simon O, Floriani M, Lobinski R, Frelon S (2014) Different uranium distribution patterns in cytosolic protein pool of zebrafish gills after chronic and acute waterborne exposures. Chemosphere 111:412–417PubMedCrossRefPubMedCentralGoogle Scholar
  17. Carlson-Lynch H, Beck BD, Boardman PD (1994) Arsenic risk assessment. Environ Health Perspect 102:354–356PubMedPubMedCentralCrossRefGoogle Scholar
  18. Chen C-J, Chuang Y-C, You S-L, Lin T-M, Wu H-Y (1986) A retrospective study on malignant neoplasms of bladder, lung and liver in Blackfoot disease endemic area in Taiwan. Br J Cancer 53:399–405PubMedPubMedCentralCrossRefGoogle Scholar
  19. Contreras-Acuña M, García-Barrera T, García-Sevillano MA, Gómez-Ariza JL (2014) Arsenic metabolites in human serum and urine after seafood (Anemonia sulcata) consumption and bioaccessibility assessment using liquid chromatography coupled to inorganic and organic mass spectrometry. Microchem J 112:56–64CrossRefGoogle Scholar
  20. Contreras-Acuña M, García-Barrera T, García-Sevillano MA, Gómez-Ariza JL (2013) Speciation of arsenic in marine food (Anemonia sulcata) by liquid chromatography coupled to inductively coupled plasma mass spectrometry and organic mass spectrometry. J Chromatogr A 1282:133–141PubMedCrossRefPubMedCentralGoogle Scholar
  21. da Silva MAO, Arruda MAZ (2012) Identification of selenium in the leaf protein of sunflowers by a combination of 2D-PAGE and laser ablation ICP-MS. Microchim Acta 176:131–136CrossRefGoogle Scholar
  22. Dasgupta T, Hebbel RP, Kaul DK (2006) Protective effect of arginine on oxidative stress in transgenic sickle mouse models. Free Radic Biol Med 41:1771–1780PubMedPubMedCentralCrossRefGoogle Scholar
  23. Del Razo LM, García-Vargas GG, Vargas H, Albores A, Gonsebatt ME, Montero R, Ostrosky-Wegman P, Kelsh M, Cebrián ME (1997) Altered profile of urinary arsenic metabolites in adults with chronic arsenicism. A pilot study. Arch Toxicol 71:211–217PubMedCrossRefPubMedCentralGoogle Scholar
  24. Dudley RE, Gammal LM, Klaassen CD (1985) Cadmium-induced hepatic and renal injury in chronically exposed rats: likely role of hepatic cadmium-metallothionein in nephrotoxicity. Toxicol Appl Pharmacol 77:414–426PubMedCrossRefPubMedCentralGoogle Scholar
  25. Early JL Jr, Schnell RC (1981) Selenium antagonism of cadmium-induced inhibition of hepatic drug metabolism in the male rat. Toxicol Appl Pharmacol 58:57–66PubMedCrossRefPubMedCentralGoogle Scholar
  26. Elinder C-G, Kjellstrom T, Hogstedt C, Andersson K, Spång G (1985) Cancer mortality of cadmium workers. Br J Ind Med 42:651–655PubMedPubMedCentralGoogle Scholar
  27. Fattorini D, Notti A, Regoli F (2006) Characterization of arsenic content in marine organisms from temperate, tropical, and polar environments. Chem Ecol 22:405–414CrossRefGoogle Scholar
  28. Flora SJS, Behari JR, Ashquin M, Tandon SK (1982) Time-dependent protective effect of selenium against cadmium-induced nephrotoxicity and hepatotoxicity. Chem Biol Interact 42:345–351PubMedCrossRefPubMedCentralGoogle Scholar
  29. Fridovich I (1995) Superoxide radical and superoxide dismutases. Annu Rev Biochem 64:97–112PubMedCrossRefPubMedCentralGoogle Scholar
  30. García-Chávez E, Santamaría A, Díaz-Barriga F, Mandeville P, Juárez BI, Jiménez-Capdeville ME (2003) Arsenite-induced formation of hydroxyl radical in the striatum of awake rats. Brain Res 976:82–89PubMedCrossRefPubMedCentralGoogle Scholar
  31. García-Sevillano MA, González-Fernández M, Jara-Biedma R, García-Barrera T, López-Barea J, Pueyo C, Gómez-Ariza JL (2012a) Biological response of free-living mouse Mus spretus from Doñana National Park under environmental stress based on assessment of metal-binding biomolecules by SEC-ICP-MS. Anal Bioanal Chem 404:1967–1981PubMedCrossRefPubMedCentralGoogle Scholar
  32. García-Sevillano MA, González-Fernández M, Jara-Biedma R, García-Barrera T, Vioque-Fernández A, López-Barea J, Pueyo C, Gómez-Ariza JL (2012b) Speciation of arsenic metabolites in the free-living mouse Mus spretus from Doñana National Park used as a bio-indicator for environmental pollution monitoring. Chem Pap 66:914CrossRefGoogle Scholar
  33. García-Sevillano MA, García-Barrera T, Navarro F, Gómez-Ariza JL (2013a) Analysis of the biological response of mouse liver (Mus musculus) exposed to As2O3 based on integrated -omics approaches. Metallomics 5:1644–1655PubMedCrossRefPubMedCentralGoogle Scholar
  34. García-Sevillano MA, Jara-Biedma R, González-Fernández M, García-Barrera T, Gómez-Ariza JL (2013b) Metal interactions in mice under environmental stress. Biometals 26:651–666PubMedCrossRefPubMedCentralGoogle Scholar
  35. García-Sevillano MA, García-Barrera T, Gómez-Ariza JL (2013c) Development of a new column switching method for simultaneous speciation of selenometabolites and selenoproteins in human serum. J Chromatogr A 1318:171–179PubMedCrossRefPubMedCentralGoogle Scholar
  36. García-Sevillano MA, García-Barrera T, Gómez-Ariza JL (2014a) Application of metallomic and metabolomic approaches in exposure experiments on laboratory mice for environmental metal toxicity assessment. Metallomics 6:237–248PubMedCrossRefPubMedCentralGoogle Scholar
  37. García-Sevillano MA, García-Barrera T, Navarro F, Gailer J, Gómez-Ariza JL (2014b) Use of elemental and molecular-mass spectrometry to assess the toxicological effects of inorganic mercury in the mouse Mus musculus. Anal Bioanal Chem 406:5853–5865PubMedCrossRefPubMedCentralGoogle Scholar
  38. García-Sevillano MA, García-Barrera T, Navarro F, Gómez-Ariza JL (2014c) Cadmium toxicity in Mus musculus mice based on a metallomic study. Antagonistic interaction between se and cd in the bloodstream. Metallomics 6:672–681PubMedCrossRefPubMedCentralGoogle Scholar
  39. García-Sevillano MT, García-Barrera T, Navarro-Roldán F, Montero-Lobato Z, Gómez-Ariza JL (2014d) 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. J Proteome 104:66–79CrossRefGoogle Scholar
  40. García-Sevillano MA, García-Barrera T, Gómez-Ariza JL (2014e) Simultaneous speciation of selenoproteins and selenometabolites in plasma and serum by dual size exclusion-affinity chromatography with online isotope dilution inductively coupled plasma mass spectrometry. Anal Bioanal Chem 406:2719–2725PubMedCrossRefPubMedCentralGoogle Scholar
  41. García-Sevillano MA, García-Barrera T, Navarro F, Gómez-Ariza JL (2014f) Absolute quantification of superoxide dismutase in cytosol and mitochondria of mice hepatic cells exposed to mercury by a novel metallomic approach. Anal Chim Acta 842:42–50PubMedCrossRefPubMedCentralGoogle Scholar
  42. García-Sevillano MA, Contreras-Acuña M, García-Barrera T, Navarro F, Gómez-Ariza JL (2014g) Metabolomic study in plasma, liver and kidney of mice exposed to inorganic arsenic based on mass spectrometry. Anal Bioanal Chem 406:1455–1469PubMedCrossRefPubMedCentralGoogle Scholar
  43. García-Sevillano MÁ, García-Barrera T, Gómez-Ariza JL (2015a) Environmental metabolomics: biological markers for metal toxicity. Electrophoresis 36:2348–2365CrossRefPubMedGoogle Scholar
  44. García-Sevillano MA, García-Barrera T, Navarro F, Abril N, Pueyo C, López-Barea J, Gómez-Ariza JL (2015b) Combination of direct infusion mass spectrometry and gas chromatography mass spectrometry for toxicometabolomic study of red blood cells and serum of mice Mus musculus after mercury exposure. J Chromatogr B Analyt Technol Biomed Life Sci 985:75–84PubMedCrossRefPubMedCentralGoogle Scholar
  45. García-Sevillano MA, García-Barrera T, Navarro F, Montero-Lobato Z, Gómez-Ariza JL (2015c) Shotgun metabolomic approach based on mass spectrometry for hepatic mitochondria of mice under arsenic exposure. Biometals 28:341–351PubMedCrossRefPubMedCentralGoogle Scholar
  46. Geiszinger AE, Goessler W, Francesconi KA (2002) The marine polychaete Arenicola marina: its unusual arsenic compound pattern and its uptake of arsenate from seawater. Mar Environ Res 53:37–50PubMedCrossRefPubMedCentralGoogle Scholar
  47. Gierasch LM, Gershenson A (2009) Post-reductionist protein science, or putting humpty dumpty back together again. Nat Chem Biol 5:774–777PubMedPubMedCentralCrossRefGoogle Scholar
  48. Girotti AW (1985) Mechanisms of lipid peroxidation. J Free Radic Biol Med 1:87–95PubMedCrossRefPubMedCentralGoogle Scholar
  49. Gómez-Ariza JL, Jahromi EZ, González-Fernández M, García-Barrera T, Gailer J (2011) Liquid chromatography-inductively coupled plasma-based metallomic approaches to probe health-relevant interactions between xenobiotics and mammalian organisms. Metallomics 3:566–577PubMedCrossRefPubMedCentralGoogle Scholar
  50. Gonzalez-Fernández M, García-Sevillano MA, Jara-Biedma R, García-Barrera T, Vioque A, López-Barea J, Pueyo C, Gómez-Ariza JL (2011) Size characterization of metal species in liver and brain from free-living (Mus spretus) and laboratory (Mus Musculus) mice by SEC-ICP-MS: application to environmental contamination assessment. J Anal At Spectrom 26:141–149CrossRefGoogle Scholar
  51. Goulet RR, Fortin C, Spry DJ (2011) Uranium. Fish Physiol 31:391–428CrossRefGoogle Scholar
  52. Grimalt JO, Ferrer M, MacPherson E (1999) The mine tailing accident in Aznalcollar. Sci Total Environ 242:3–11PubMedCrossRefPubMedCentralGoogle Scholar
  53. Gunn SA, Gould TC, Anderson WAD (1963) Cadmium-induced interstitial cell tumors in rats and mice and their prevention by zinc. J Natl Cancer Inst 31:745–749PubMedPubMedCentralGoogle Scholar
  54. Haddow A, Roe FJ, Dukes CE, Mitchley AC (1964) Cadmium neoplasia: sarcomata at the site of injection of cadmium sulphate in rats and mice. Br J Cancer 18:667–673PubMedPubMedCentralCrossRefGoogle Scholar
  55. Hems DA (1972) Metabolism of glutamine and glutamic acid by isolated perfused kidneys of normal and acidotic rats. Biochem J 130:671–680PubMedPubMedCentralCrossRefGoogle Scholar
  56. Hinojosa Reyes L, Marchante-Gayón JM, García Alonso JI, Sanz-Medel A (2003) Quantitative speciation of selenium in human serum by affinity chromatography coupled to post-column isotope dilution analysis ICP-MS. J Anal At Spectrom 18:1210–1216CrossRefGoogle Scholar
  57. Hughes MF, Kenyon EM, Edwards BC, Mitchell CT, Del Razo LM, Thomas DJ (2003) Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate. Toxicol Appl Pharmacol 191:202–210PubMedCrossRefPubMedCentralGoogle Scholar
  58. Jara-Biedma R, González-Dominguez R, García-Barrera T, Lopez-Barea J, Pueyo C, Gómez-Ariza JL (2013) Evolution of metallothionein isoforms complexes in hepatic cells of Mus musculus along cadmium exposure. Biometals 26:639–650PubMedCrossRefPubMedCentralGoogle Scholar
  59. Jin Y, Zhao F, Zhong Y, Yu X, Sun D, Liao Y, Lv X, Li G, Sun G (2010) Effects of exogenous GSH and methionine on methylation of inorganic arsenic in mice exposed to arsenite through drinking water. Environ Toxicol 25:361–366PubMedCrossRefPubMedCentralGoogle Scholar
  60. Jitaru P, Goenaga-Infante H, Vaslin-Reimann S, Fisicaro P (2010) A systematic approach to the accurate quantification of selenium in serum selenoalbumin by HPLC-ICP-MS. Anal Chim Acta 657:100–107PubMedCrossRefPubMedCentralGoogle Scholar
  61. Jitaru P, Prete M, Cozzi G, Turetta C, Cairns W, Seraglia R, Traldi P, Cescon P, Barbante C (2008) Speciation analysis of selenoproteins in human serum by solid-phase extraction and affinity HPLC hyphenated to ICP-quadrupole MS. J Anal At Spectrom 23:402–406CrossRefGoogle Scholar
  62. Kasai H (1997) Analysis of a form of oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res 387:147–163PubMedCrossRefPubMedCentralGoogle Scholar
  63. Kitchin KT, Wallace K (2005) Arsenite binding to synthetic peptides based on the Zn finger region and the estrogen binding region of the human estrogen receptor-α. Toxicol Appl Pharmacol 206:66–72PubMedCrossRefPubMedCentralGoogle Scholar
  64. Kitchin KT, Wallace K (2008) The role of protein binding of trivalent arsenicals in arsenic carcinogenesis and toxicity. J Inorg Biochem 102:532–539PubMedCrossRefPubMedCentralGoogle Scholar
  65. Knauer B, Majka P, Watkins KJ, Taylor AWR, Malamanova D, Paul B, Yu H-H, Bush AI, Hare DJ, Reser DH (2017) Whole-brain metallomic analysis of the common marmoset (: Callithrix jacchus). Metallomics 9:411–423PubMedCrossRefPubMedCentralGoogle Scholar
  66. Kolonel LN (1976) Association of cadmium with renal cancer. Cancer 37:1782–1787PubMedCrossRefPubMedCentralGoogle Scholar
  67. Lu M, Wang H, Li X-F, Arnold LL, Cohen SM, Le XC (2007) Binding of dimethylarsinous acid to Cys-13α of rat hemoglobin is responsible for the retention of arsenic in rat blood. Chem Res Toxicol 20:27–37PubMedCrossRefPubMedCentralGoogle Scholar
  68. Maciel BCM, Barbosa HS, Pessôa GS, Salazar MM, Pereira GAG, Gonçalves DC, Ramos CHI, Arruda MAZ (2014) Comparative proteomics and metallomics studies in Arabidopsis thaliana leaf tissues: evaluation of the selenium addition in transgenic and nontransgenic plants using two-dimensional difference gel electrophoresis and laser ablation imaging. Proteomics 14:904–912PubMedCrossRefPubMedCentralGoogle Scholar
  69. Maret W (2004) Exploring the zinc proteome. J Anal At Spectrom 19:15–19CrossRefGoogle Scholar
  70. Martelli A, Rousselet E, Dycke C, Bouron A, Moulis J-M (2006) Cadmium toxicity in animal cells by interference with essential metals. Biochimie 88:1807–1814PubMedCrossRefPubMedCentralGoogle Scholar
  71. Messaoudi I, El Heni J, Hammouda F, Saïd K, Kerkeni A (2009) Protective effects of selenium, zinc, or their combination on cadmium-induced oxidative stress in rat kidney. Biol Trace Elem Res 130:152–161PubMedCrossRefPubMedCentralGoogle Scholar
  72. Montes-Nieto R, Fuentes-Almagro CA, Bonilla-Valverde D, Prieto-Alamo MJ, Jurado J, Carrascal M, Gómez-Ariza JL, López-Barea J, Pueyo C (2007) Proteomics in free-living Mus spretus to monitor terrestrial ecosystems. Proteomics 7:4376–4387PubMedCrossRefPubMedCentralGoogle Scholar
  73. Montes Nieto R, García-Barrera T, Gómez-Ariza JL, López-Barea J (2010) Environmental monitoring of Domingo Rubio stream (Huelva estuary, SW Spain) by combining conventional biomarkers and proteomic analysis in Carcinus maenas. Environ Pollut 158:401–408PubMedCrossRefPubMedCentralGoogle Scholar
  74. Mounicou S, Szpunar J, Lobinski R (2009) Metallomics: the concept and methodology. Chem Soc Rev 38:1119–1138PubMedCrossRefPubMedCentralGoogle Scholar
  75. Naranmandura H, Suzuki KT (2008) Formation of dimethylthioarsenicals in red blood cells. Toxicol Appl Pharmacol 227:390–399PubMedCrossRefPubMedCentralGoogle Scholar
  76. Nicholson JK, Timbrell JA, Sadler PJ (1985) Proton NMR spectra of urine as indicators of renal damage. Mercury-induced nephrotoxicity in rats. Mol Pharmacol 27:644–651PubMedPubMedCentralGoogle Scholar
  77. Nischwitz V, Davies JT, Marshall D, González M, Gómez Ariza JL, Goenaga-Infante H (2013) Speciation studies of vanadium in human liver (HepG2) cells after in vitro exposure to bis(maltolato)oxovanadium(iv) using HPLC online with elemental and molecular mass spectrometry. Metallomics 5:1685–1697PubMedCrossRefPubMedCentralGoogle Scholar
  78. Nuevo Ordoñez Y, Montes-Bayón M, Blanco-González E, Sanz-Medel A (2010) Quantitative analysis and simultaneous activity measurements of cu, Zn-superoxide dismutase in red blood cells by HPLC-ICPMS. Anal Chem 82:2387–2394PubMedCrossRefPubMedCentralGoogle Scholar
  79. Ogra Y, Nagasaki S, Yawata A, Anan Y, Hamada K, Mizutani A (2016) Metallomics approach to changes in element concentration during differentiation from fibroblasts into adipocytes by element array analysis. J Toxicol Sci 41:241–244PubMedCrossRefPubMedCentralGoogle Scholar
  80. Outten CE, O’Halloran TV (2001) Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis. Science 292:2488–2492PubMedCrossRefPubMedCentralGoogle Scholar
  81. Palacios Ò, Encinar JR, Bertin G, Lobinski R (2005) Analysis of the selenium species distribution in cow blood by size exclusion liquid chromatography-inductively coupled plasma collision cell mass spectrometry (SEC-ICPccMS). Anal Bioanal Chem 383:516–522PubMedCrossRefPubMedCentralGoogle Scholar
  82. Palacios O, Lobinski R (2007) Investigation of the stability of selenoproteins during storage of human serum by size-exclusion LC-ICP-MS. Talanta 71:1813–1816PubMedCrossRefPubMedCentralGoogle Scholar
  83. Paquet F, Houpert P, Blanchardon E, Delissen O, Maubert C, Dhieux B, Moreels AM, Frelon S, Voisin P, Gourmelon P (2006) Accumulation and distribution of uranium in rats after chronic exposure by ingestion. Health Phys 90:139–147PubMedCrossRefPubMedCentralGoogle Scholar
  84. Piao F, Ma N, Hiraku Y, Murata M, Oikawa S, Cheng F, Zhong L, Yamauchi T, Kawanishi S, Yokoyama K (2005) Oxidative DNA damage in relation to neurotoxicity in the brain of mice exposed to arsenic at environmentally relevant levels. J Occup Health 47:445–449PubMedCrossRefPubMedCentralGoogle Scholar
  85. Piasek M, Blanuša M, Kostial K, Laskey JW (2001) Placental cadmium and progesterone concentrations in cigarette smokers. Reprod Toxicol 15:673–681PubMedCrossRefPubMedCentralGoogle Scholar
  86. Platell C, Kong S-E, McCauley R, Hall JC (2000) Branched-chain amino acids. J Gastroenterol Hepatol 15:706–717PubMedCrossRefPubMedCentralGoogle Scholar
  87. Portbury SD, Hare DJ, Sgambelloni CJ, Bishop DP, Finkelstein DI, Doble PA, Adlard PA (2017) Age modulates the injury-induced metallomic profile in the brain. Metallomics 9:402–410PubMedCrossRefPubMedCentralGoogle Scholar
  88. Rodríguez-González P, Marchante-Gayón JM, García Alonso JI, Sanz-Medel A (2005) Isotope dilution analysis for elemental speciation: a tutorial review. Spectrochim Acta Part B: Spectrosc 60:151–207CrossRefGoogle Scholar
  89. Ruiz-Laguna J, Abril N, García-Barrera T, Gómez-Ariza JL, López-Barea J, Pueyo C (2006) Absolute transcript expression signatures of Cyp and Gst genes in Mus spretus to detect environmental contamination. Environ Sci Technol 40:3646–3652PubMedCrossRefPubMedCentralGoogle Scholar
  90. Saïd L, Banni M, Kerkeni A, Saïd K, Messaoudi I (2010) Influence of combined treatment with zinc and selenium on cadmium induced testicular pathophysiology in rat. Food Chem Toxicol 48:2759–2765PubMedCrossRefPubMedCentralGoogle Scholar
  91. Shigeta K, Sato K, Furuta N (2007) Determination of selenoprotein P in submicrolitre samples of human plasma using micro-affinity chromatography coupled with low flow ICP-MS. J Anal At Spectrom 22:911–916CrossRefGoogle Scholar
  92. Shimoda R, Achanzar WE, Qu W, Nagamine T, Takagi H, Mori M, Waalkes MP (2003) Metallothionein is a potential negative regulator of apoptosis. Toxicol Sci 73:294–300PubMedCrossRefPubMedCentralGoogle Scholar
  93. Srivastava RC, Ahmad I, Kaur G, Hasan SK (1988) Alterations in the metabolism of endogenous trace metals due to cadmium, manganese and nickel-effect of partial hepatectomy. J Environ Sci Health Part A: Environ Sci Eng 23:95–101CrossRefGoogle Scholar
  94. Stadtman ER (1992) Protein oxidation and aging. Science 257:1220–1224PubMedCrossRefPubMedCentralGoogle Scholar
  95. Sussulini A, Becker JS, Becker JS (2017) Laser ablation ICP-MS: application in biomedical research. Mass Spectrom Rev 36:47–57PubMedCrossRefPubMedCentralGoogle Scholar
  96. Suzuki KT (2005) Metabolomics of arsenic based on speciation studies. Anal Chim Acta 540:71–76CrossRefGoogle Scholar
  97. Suzuki KT, Mandal BK, Ogra Y (2002) Speciation of arsenic in body fluids. Talanta 58:111–119PubMedCrossRefPubMedCentralGoogle Scholar
  98. Suzuki KT, Ogra Y (2002) Metabolic pathway for selenium in the body: speciation by HPLC-ICP MS with enriched se. Food Addit Contam 19:974–983PubMedCrossRefPubMedCentralGoogle Scholar
  99. Suzuki Y, Yoshikawa H (1981) Cadmium, copper, and zinc excretion and their binding to metallothionein in urine of cadmium exposed rats. J Toxicol Environ Health 8:479–487PubMedCrossRefPubMedCentralGoogle Scholar
  100. Szinicz L, Forth W (1988) Effect of As2O3 on gluconeogenesis. Arch Toxicol 61:444–449PubMedCrossRefPubMedCentralGoogle Scholar
  101. Szymańska-Chabowska A, Antonowicz-Juchniewicz J, Andrzejak R (2007) The concentration of selected cancer markers (TPA, TPS, CYFRA 21-1, CEA) in workers occupationally exposed to arsenic (as) and some heavy metals (Pb, cd) during a two-year observation study. Int J Occup Med Environ Health 20:229–239PubMedCrossRefPubMedCentralGoogle Scholar
  102. Tainer JA, Roberts VA, Getzoff ED (1991) Metal-binding sites in proteins. Curr Opin Biotechnol 2:582–591PubMedCrossRefPubMedCentralGoogle Scholar
  103. Thomas DJ, Styblo M, Lin S (2001) The cellular metabolism and systemic toxicity of arsenic. Toxicol Appl Pharmacol 176:127–144PubMedCrossRefPubMedCentralGoogle Scholar
  104. Vahter M (1981) Biotransformation of trivalent and pentavalent inorganic arsenic in mice and rats. Environ Res 25:286–293PubMedCrossRefPubMedCentralGoogle Scholar
  105. Vahter M, Norin H (1980) Metabolism of 74As-labeled trivalent and pentavalent inorganic arsenic in mice. Environ Res 21:446–457PubMedCrossRefPubMedCentralGoogle Scholar
  106. Vioque-Fernández A, Alves de Almeida E, López-Barea J (2009) Assessment of Doñana National Park contamination in Procambarus clarkii: integration of conventional biomarkers and proteomic approaches. Sci Total Environ 407:1784–1797PubMedCrossRefPubMedCentralGoogle Scholar
  107. Wang H, Wu Z, Chen B, He M, Hu B (2015) Chip-based array magnetic solid phase microextraction on-line coupled with inductively coupled plasma mass spectrometry for the determination of trace heavy metals in cells. Analyst 140:5619–5626PubMedCrossRefPubMedCentralGoogle Scholar
  108. Wang Y, Tang H, Nicholson JK, Hylands PJ, Sampson J, Holmes E (2005) A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.) ingestion. J Agric Food Chem 53:191–196PubMedCrossRefPubMedCentralGoogle Scholar
  109. Warner ML, Moore LE, Smith MT, Fanning E, Smith AH, Kalman DA (1994) Increased micronuclei in exfoliated bladder cells of individuals who chronically ingest arsenic-contaminated water in Nevada. Cancer Epidemiol Biomark Prev 3:583–590Google Scholar
  110. Wei L, Liao P, Wu H, Li X, Pei F, Li W, Wu Y (2008) Toxicological effects of cinnabar in rats by NMR-based metabolic profiling of urine and serum. Toxicol Appl Pharmacol 227:417–429PubMedCrossRefPubMedCentralGoogle Scholar
  111. Wolters DA, Stefanopoulou M, Dyson PJ, Groessl M (2012) Combination of metallomics and proteomics to study the effects of the metallodrug RAPTA-T on human cancer cells. Metallomics 4:1185–1196PubMedCrossRefPubMedCentralGoogle Scholar
  112. Wrobel K, Wrobel K, Caruso JA (2009) Epigenetics: an important challenge for ICP-MS in metallomics studies. Anal Bioanal Chem 393:481–486PubMedCrossRefPubMedCentralGoogle Scholar
  113. Xu M, Bijoux H, Gonzalez P, Mounicou S (2014a) Investigating the response of cuproproteins from oysters (Crassostrea gigas) after waterborne copper exposure by metallomic and proteomic approaches. Metallomics 6:338–346PubMedCrossRefPubMedCentralGoogle Scholar
  114. Xu M, Frelon S, Simon O, Lobinski R, Mounicou S (2014b) Non-denaturating isoelectric focusing gel electrophoresis for uranium-protein complexes quantitative analysis with LA-ICP MS. Anal Bioanal Chem 406:1063–1072PubMedCrossRefPubMedCentralGoogle Scholar
  115. Xu M, Frelon S, Simon O, Lobinski R, Mounicou S (2014c) Development of a non-denaturing 2D gel electrophoresis protocol for screening in vivo uranium-protein targets in Procambarus clarkii with laser ablation ICP MS followed by protein identification by HPLC-Orbitrap MS. Talanta 128:187–195PubMedCrossRefPubMedCentralGoogle Scholar
  116. Yáñez L, Carrizales L, Zanatta MT, de Jesús Mejía J, Batres L, Díaz-Barriga F (1991) Arsenic-cadmium interaction in rats: toxic effects in the heart and tissue metal shifts. Toxicology 67:227–234PubMedCrossRefPubMedCentralGoogle Scholar
  117. Zalups RK (2000) Molecular interactions with mercury in the kidney. Pharmacol Rev 52:113–143PubMedPubMedCentralGoogle Scholar
  118. Zalups RK, Koropatnick J (2000) Temporal changes in metallothionein gene transcription in rat kidney and liver: relationship to content of mercury and metallothionein protein. J Pharmacol Exp Ther 295:74–82PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Gema Rodríguez-Moro
    • 1
    • 2
    • 3
  • Sara Ramírez-Acosta
    • 1
    • 2
    • 3
  • Ana Arias-Borrego
    • 1
    • 2
    • 3
  • Tamara García-Barrera
    • 1
    • 2
    • 3
  • José Luis Gómez-Ariza
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Chemistry, Faculty of Experimental SciencesUniversity of Huelva, Campus de El CarmenHuelvaSpain
  2. 2.Research Center on Natural Resources, Health and the Environment (RENSMA), University of HuelvaHuelvaSpain
  3. 3.International Campus of Excellence on Agrofood (ceiA3), University of HuelvaHuelvaSpain

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