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Systematic study of the selenium fractionation in human plasma from a cancer prevention trial using HPLC hyphenated to ICP-MS and ESI-MS/MS

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Abstract

This work represents the first systematic speciation study of selenium (Se) in plasma from subjects participating in a pilot study for a cancer prevention trial (PRECISE). This involved supplementation of elderly British and Danish individuals with selenised yeast for 6 months and 5 years, respectively, at 100, 200, and 300 μg Se/day or placebo. Speciation data was obtained for male plasma using HPLC-ICP-MS and HPLC-ESI-MS/MS. With the proposed strategy, approximately 1.5 mL of plasma was needed to determine total Se concentration and the fractionation of Se in high molecular weight (HMW) and low molecular weight (LMW) pools, and for quantification and identification of small Se species. For the first time, Se-methyl-selenocysteine (MSC) and methyl-2-acetamido-2deoxy1-seleno-β-d-galactopyranoside (Selenosugar-1) were structurally confirmed in plasma after supplementation with selenised yeast within the studied range. Determination of selenomethionine (SeMet) incorporated non-specifically into albumin (SeALB) was achieved by HPLC-ICP-MS after hydrolysis. By subtracting this SeMet concentration from the total Se in the HMW pool, the concentration of Se incorporated into selenoproteins was calculated. Results from the speciation analysis of the free Se metabolite fraction (5% of total plasma Se) suggest a significant increase in the percentage of Se (as SeMet plus Selenosugar-1) of up to 80% of the total Se in the LMW fraction after 6 months of supplementation. The Se distribution in the HMW fraction reflects a significant increase in SeALB with Se depletion from selenoproteins, which occurs most significantly at doses of over 100 μg Se/day after 5 years. The results of this work will inform future trial design.

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Acknowledgements

Thanks go to Bryan McCullough, Camilla Liscio, and Volker Nischwitz for their help with the determination of Selenosugar-1 by ESI-MS/MS. We also like to thank M. Estela del Castillo Busto for valuable discussions before and during the preparation of this manuscript. We acknowledge the donations of the Danish trial samples for further studies from Pharma Nord Asp as part of a commercial project.

Funding

The authors receive funding for their work from the UK National Measurement System Chemical and Biological Measurement Program, funded by the Department of Business, Energy & Industrial Strategy.

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Authors and Affiliations

  1. LGC Limited, Queens Road, Teddington, Middlesex, TW11 0LY, UK

    Christian L. Ward-Deitrich, Emily Whyte, Christopher Hopley & Heidi Goenaga-Infante

  2. Department of Nutritional Sciences, University of Surrey, Guildford, GU2 7XH, UK

    Margaret P. Rayman

  3. Laboratory of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo, Chiba, 260-8675, Japan

    Yasumitsu Ogra

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  1. Christian L. Ward-Deitrich
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Corresponding author

Correspondence to Heidi Goenaga-Infante.

Ethics declarations

The UK PRECISE Pilot Trial (NCT00022165) had approval from UK Local Research Ethics Committees (South Tees (ref: 99/69), Worcestershire Health Authority (ref: LREC 74/99), Norwich District (ref: LREC 99/141), Great Yarmouth and Waveney (under reciprocal arrangements with Norwich District LREC)), and participants provided written informed consent. The Denmark PRECISE pilot study (ClinicalTrials.gov ID: NCT01819649) was approved by regional Data Protection Agency and Scientific Ethics Committees of Vejle and Funen counties.

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Ward-Deitrich, C.L., Whyte, E., Hopley, C. et al. Systematic study of the selenium fractionation in human plasma from a cancer prevention trial using HPLC hyphenated to ICP-MS and ESI-MS/MS. Anal Bioanal Chem 413, 331–344 (2021). https://doi.org/10.1007/s00216-020-02988-9

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