title: Comparison of different selenocompounds with respect to nutritional value vs. toxicity using liver cells in culture.
abstract: The essential micronutrient selenium (Se) exerts its biological effects mainly through enzymatically active selenoproteins. Their biosynthesis depends on the 21st proteinogenic amino acid selenocysteine and thus on dietary Se supply. Hepatically derived selenoprotein P (SEPP) is the central selenoprotein in blood controlling Se transport and distribution. Kidney-derived extracellular glutathione peroxidase is another relevant serum selenoprotein depending on SEPP for biosynthesis. Therefore, secretion of SEPP by hepatocytes is crucial to convert nutritional sources into serum Se, supporting Se status and selenoprotein biosynthesis in other tissues. In order to compare the bioactivity of 10 different selenocompounds, their dose-dependent toxicities and nutritional qualities to support SEPP and glutathione peroxidase biosynthesis were determined in a murine and two human liver cell lines. Characteristic dose- and time-dependent effects on viability and SEPP production were observed. Incubations with 100 nM sodium selenite, l- or dl-selenocystine, selenodiglutathione or selenomethyl-selenocysteine increased SEPP concentrations in the culture medium up to 6.5-fold over control after 72 h. In comparison, sodium selenate, l- or dl-selenomethionine or methylseleninic acid was less effective and increased SEPP by 2.5-fold under these conditions. As expected, ebselen did not increase selenoprotein production, supporting its classification as a stable selenocompound. Methylseleninic acid, l-selenocystine, selenodiglutathione or selenite induced cell death in micromolar concentrations, whereas selenomethionine or ebselen was not toxic within the concentration range tested. Our results indicate that hepatic selenoprotein production and toxicity of selenocompounds do not correlate with and rather represent compound-specific properties. The favourable profile of selenomethylselenocysteine warrants its consideration as a promising option for supplementation purposes.
authors.affiliation: Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, CVK, Südring, Berlin, Germany.
authors.forename: Carolin S
authors.initials: CS
authors.lastname: Hoefig
authors.forename: Kostja
authors.initials: K
authors.lastname: Renko
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.forename: Marc
authors.initials: M
authors.lastname: Birringer
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
mesh_terms: D000818:Animals; D003553:Cystine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D019587:Dietary Supplements; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009753:Nutritive Value; D016566:Organoselenium Compounds / Q000494:pharmacology* / Q000633:toxicity; D051149:Selenoprotein P / Q000235:genetics / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology / Q000633:toxicity
chemical_list: D016566:Organoselenium Compounds; D051149:Selenoprotein P; C009226:selenocystine; C017710:selenodiglutathione; D003553:Cystine; C008493:methylselenic acid; D005978:Glutathione; D018038:Sodium Selenite