Side‐Directed Transfer and Presystemic Metabolism of Selenoneine in a Human Intestinal Barrier Model

Abstract

Scope: Selenoneine, a recently discovered selenium (Se) species mainly present in marine fish, is the Se analogue of ergothioneine, a sulfur-containing purported antioxidant. Although similar properties have been proposed for selenoneine, data on its relevance to human health are yet scarce. Here, the transfer and presystemic metabolism of selenoneine in an in vitro model of the human intestinal barrier are investigated. Methods and results: Selenoneine and the reference species Se-methylselenocysteine (MeSeCys) and selenite are applied to the Caco-2 intestinal barrier model. Selenoneine is transferred in higher amounts, but with similar kinetics as selenite, while MeSeCys shows the highest permeability. In contrast to the reference species, transfer of selenoneine is directed toward the blood side. Cellular Se contents demonstrate that selenoneine is efficiently taken up by Caco-2 cells. Moreover, HPLC/MS-based Se speciation studies reveal a partial metabolism to Se-methylselenoneine, a metabolite previously detected in human blood and urine. Conclusions: Selenoneine is likely to pass the intestinal barrier via transcellular, carrier-mediated transport, is highly bioavailable to Caco-2 cells and undergoes metabolic transformations. Therefore, further studies are needed to elucidate its possible health effects and to characterize the metabolism of selenoneine in humans.

Total Synthesis and Functional Characterization of Selenoneine

“…50–100 μL min −1 mg protein −1 ) for ergothioneine and ETTh in our expression system. Nevertheless these data support the idea that selenoneine is efficiently distributed in the human body even at low concentrations …”

“…Selenoneine also accumulates in humans with a seafood‐rich diet which raises questions about potential health risks or benefits emanating from this unusual selenium source . However, aside of intriguing indications that selenoneine may provide protection against mercury poisoning, little is known about the chemistry of such compounds …”

“…[16][17] However, aside of intriguing indications that selenoneine may provide protection against mercury poisoning, [16,18] little is known about the chemistry of such compounds. [19] In the quest of learning more, we developed the first chemical synthesis of unprotected 2-selenoimidazoles. Based on this methodology we synthesized selenoneine and characterized its properties in comparison with ergothioneine ( Figure 1a).…”

The biology of ergothioneine, an antioxidant nutraceutical

“…•− (38) . Its Se equivalent is known as selenoneine and also has strong antioxidant properties (45)(46)(47)(48)(49)(50)(51)(52) , but is not otherwise discussed here. From a pharmaco-chemical point of view ERG is also unusual, sinceusing our standard substructure analysis (53,54) in KNIME (55) we note that just two drugs marketed for human consumption (the anti-thyroxine-production drug methimazole and its pro-drug carbimazole, Fig.…”

Total Synthesis and Functional Characterization of Selenoneine

“…[16,17] However,a side of intriguing indications that selenoneine may provide protection against mercury poisoning, [16,18] little is known about the chemistry of such compounds. [19] In the quest of learning more,w ed eveloped the first chemical synthesis of unprotected 2-selenoimidazoles.B ased on this methodology we synthesized selenoneine and charac- terized its properties in comparison with ergothioneine ( Figure 1a).…”