Protein-Conjugated 1β-Seleno-N-Acetyl-D-Galactosamine Plays Key Roles in Selenium Transport and Storage in Rats and...

The nutritional availability and toxicity of Selenium (Se) compounds vary considerably. We previously identified 2 N-acetyl-D-galactosamine-conjugated Se forms: 1β-methylseleno-N-acetyl-D-galactosamine (a methylated urinary metabolite) and 1β-seleno-N-acetyl-D-galactosamine (reduced selenosugar; a nonmethylated precursor).

The aim of this study is to evaluate the reduced selenosugar, currently regarded as a precursor for urinary Se excretion, as a potential nutritional Se source.

Oxidized selenosugar was chemically synthesized, and it was administered to Se-deficient and Se-adequate male Wistar rats (8 wk old) by tail vein injection for 2 d (10 μg Se/d). Serum, urine, and various organs were analyzed by inductively coupled plasma mass spectrometry to quantify Se species and selenoproteins. Cytotoxicity was examined in HepG2 cells treated with 5 to 1000 μM oxidized selenosugar for 24 to 48 h, and cell viability was determined. Statistical differences were assessed by Tukey's test.

In Se-deficient rats, administration of oxidized selenosugar significantly restored serum glutathione (GSH) peroxidase 3 and selenoprotein P levels to 33% to 68% of those in Se-adequate controls, whereas selenite restored them to 42% to 74%. In HepG2 cells, oxidized selenosugar exhibited no cytotoxicity at concentrations ≤1000 μM, whereas selenite markedly reduced cell viability at concentrations above 5 μM (P < 0.05). Moreover, the reduced selenosugar was detected in liver, kidney, serum, and small intestine, partly conjugated with cysteine via selenylsulfide bonds, suggesting a role in Se storage.

These results position the reduced selenosugar as a unique Se form with dual roles in storage and transport, contributing to Se homeostasis. The originally reported chemical form of selenosugar A was defined as the GSH-conjugated form, but the present study indicates that the free selenol form may represent the physiologically active species. Our results highlight the reduced selenosugar as a previously underestimated, efficiently utilized, and safe Se source of animal origin, beyond just a urinary excretion precursor.