Biological interactions between mercury and selenium in distribution and detoxification processes in mice under controlled exposure. Effects on selenoprotein M.A. García-Sevillano a,b,c , G. Rodríguez-Moro a,b,c , T. García-Barrera a,b,c,⇑ , F. Navarro c,d , J.L. Gómez-Ariza a,b,c,⇑ a Department of Chemistry and Materials Science, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain b Research Center on Health and Environment (CYSMA), University of Huelva, Spain c International Campus of Excellence on Agrofood (ceiA3), University of Huelva, Spain d Department of Environmental Biology and Public Health, Cell Biology, Faculty of Experimental Sciences, University of Huelva, Campus El Carmen, 21007 Huelva, Spain article info Article history: Received 3 November 2014 Received in revised form 24 January 2015 Accepted 1 February 2015 Available online 7 February 2015 Keywords: Mus musculus Mercury Selenium Metal interactions Metallomics Selenoproteins abstract Antagonistic interactions between mercury (Hg) and selenium (Se), were evaluated in mouse (Mus mus- culus), as a mammalian model, in a series of controlled exposure experiments. The beneficial effect of Se against Hg toxicity involves a variety of biochemical and toxicological processes that have not been clar- ified yet. For this purpose, a metallomic workflow based on the use of size-exclusion chromatography (SEC) with inductively coupled plasma mass spectrometry (ICP-MS) detection was complemented with the speciation of selenoproteins and low molecular mass selenium species in serum and liver cytosolic extracts using a multidimensional approach based on SEC-AF-HPLC-ICPMS, using species-unspecific iso- tope dilution (SUID)-ICP-MS for selenium quantification. The results showed potential interactions between Hg/Se in organs and serum related to accumulation and detoxification processes, in addition to the effects of mercury on selenoproteins in hepatic cytosolic extracts and bloodstream when both ele- ments are administrated at the same time. These results provide information about elements distribu- tion, interactions and homeostasis and reveal the potential of metallomic approaches in exposure experiments. Ó 2015 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Mercury (Hg) is a widespread environmental and industrial con- taminant that induces rigorous toxic effects in body tissues of both human and animals [1], depending on its different chemical forms [2]. Mercury exists in three main chemical forms: elemental, as an inorganic salt, or bound to an organic ligand; although all the chem- ical species are potentially toxic. Divalent inorganic mercury (Hg 2+ ) is one of the strongest thiol-binding elements, which explains its toxicity by the ability to form stable complexes with the sulfhy- dryl-cysteine groups of proteins (–SH), such as numerous thiol- related enzymes [3]. Hg 2+ can also give rise to free radicals that induce lipid, protein and DNA oxidation related to oxidative stress [4–6]. On the other hand, organic mercury compounds are mostly metabolized in the liver where they may suffer demethylation [7] or undergo conjugation reactions with glutathione (GSH) [2,8]. It is well known that Se presents a protective effect against Hg toxic- ity and inhibits oxidative damage caused by Hg in mammals [9–11]. http://dx.doi.org/10.1016/j.cbi.2015.02.001 0009-2797/Ó 2015 Elsevier Ireland Ltd. All rights reserved. Abbreviations: AF, affinity chromatography; BSA, bovine serum albumin; CRMs, certified reference materials; Cys, cysteine; DNA, deoxyribonucleic acid; eGPx, extracellular glutathione peroxidase; GPx, glutathione peroxidase; GSH, reduced glutathione; HMM, high molecular mass; HPLC, high performance liquid chroma- tography; ICP-MS, inductively coupling plasma-mass spectrometry; IDA, isotopic dilution analysis; LC, liquid chromatography; LMM, low molecular mass; MS, mass spectrometry; MT, metallothionein; ORS, octopole reaction systems; PMSF, phen- ylmethanesulfonyl fluoride; RBCs, red blood cells; SeAlb, selenoalbumin; SEC, size exclusion chromatography; SelP, selenoprotein P; SeCys, selenocysteine; SUID, species-unspecific isotopic dilution; SOD, superoxide dismutase; ThxR, thioredoxin reductase; TCEP, tris(2-carboxyethyl)phosphine hydrochloride; 2D, two dimensional. ⇑ Corresponding authors at: Department of Chemistry and Materials Science ‘‘Professor José Carlos Vílchez Martín’’, Faculty of Experimental Sciences, University of Huelva, Campus El Carmen, 21007 Huelva, Spain. Tel.: +34 959219962; fax: +34 959219942 (T. García-Barrera). Tel.: +34 959219968; fax: +34 959219942 (J.L. Gómez-Ariza). E-mail addresses: mangel.garcia@dqcm.uhu.es (M.A. García-Sevillano), gema. moro@dqcm.uhu.es (G. Rodríguez-Moro), tamara@dqcm.uhu.es (T. García-Barrera), navarro@uhu.es (F. Navarro), ariza@uhu.es (J.L. Gómez-Ariza). Chemico-Biological Interactions 229 (2015) 82–90 Contents lists available at ScienceDirect Chemico-Biological Interactions journal homepage: www.elsevier.com/locate/chembioint