Distribution and accumulation of dietary ergothioneine and its metabolites in mouse tissues

Abstract

L-ergothioneine (ET) is a diet-derived amino acid that accumulates at high concentrations in animals and humans. Numerous studies have highlighted its antioxidant abilities in vitro, and possible cytoprotective capabilities in vivo. We investigated the uptake and distribution of ET in various organs by a highly sensitive and specific liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) technique, both before and after oral administration of pure ET (35 and 70 mg/kg/day for 1, 7, and 28 days) to male C57BL6J mice. ET primarily concentrates in the liver and whole blood, and also in spleen, kidney, lung, heart, intestines, eye, and brain tissues. Strong correlations were found between ET and its putative metabolites - hercynine, ET-sulfonate (ET-SO3H), and S-methyl ET. Hercynine accumulates in the brain after prolonged ET administration. This study demonstrates the uptake and distribution of ET and provides a foundation for future studies with ET to target oxidative damage in a range of tissues in human diseases.

Inhibition of amyloid‐induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model

“…Multiple modes of action by ET suggest that this unique dietary compound may be able to target various pathological aspects of AD. First and foremost, ET can cross the BBB, with several reports of ET in animal and human brains, and expression of the ET transporter, OCTN1 in rodent brains (cerebellum, hippocampus, and cortex) . We have also identified the presence of ET in post‐mortem human brain and cerebrospinal fluid (unpublished data).…”

“…This extension in mean and maximal lifespan with ET treatment would equate to years when translated to a human lifespan, but more importantly, the increased healthspan would lead to a significant reduction in morbidity and societal burden. It should also be noted that numerous animal and human studies have demonstrated that blood and tissue levels of ET are capable of reaching millimolar levels hence validating the feasibility of the doses tested in the nematodes .…”

Ergothioneine – a diet‐derived antioxidant with therapeutic potential

“…This could happen by multiple mechanisms of course, such as changes in diet and/or OCTN1 transporter activity. Dietary ET does cross the blood–brain barrier, since it can be measured in human cerebrospinal fluid and postmortem brain samples (our unpublished data; also see ) and readily enters the brain when administered to mice . A Japanese study has found a correlation between increased intake of mushrooms (one of the most important dietary sources of ET ; Table ) and lower incidence of dementia.…”

“…Ergothioneine can accumulate to high levels in some human and animal tissues, including red blood cells (with basal levels of ~ 125 μ m and ~ 220 μ m in human and mouse whole blood, respectively, and millimolar levels reported in red blood cells ), liver and spleen (with basal levels of ~ 350 μmol·g −1 tissue and ~ 100 μmol·g −1 tissue in mouse liver and spleen, respectively) . Our recent study demonstrated that when ET is orally administered to mice, it accumulates rapidly in the liver and blood cells but also enters most (or perhaps all) other tissues, including brain, heart, lung, kidney, spleen and eye. Since animal sera are commonly used in cell culture media, ET is even present in cell cultures.…”

“…Dietary ET in animals (including humans) is absorbed by means of an intestinal transporter, OCTN1, that has a high degree of specificity . The same transporter then distributes ET to most or all body tissues: excretion from the body is slow and administered ET is highly retained in human and other animal body tissues and red blood cells . This implies that ET has a useful function, otherwise why absorb and retain it?…”