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.
Highlights
L-ergothioneine (2-mercaptohistidine trimethylbetaine, C9H15N3O2S; ET) was discovered by Charles Tanret in the ergot fungus Claviceps purpurea[1]
Our previous work demonstrated that ET accumulates in the fibrotic liver of a guinea pig model of non-alcoholic fatty liver disease, which correlates with the progression of liver damage, suggesting a possible stress response by the injured tissue to suppress oxidative damage and delay further tissue injury[23,32]
We evaluated the mRNA expression of the ET transporter, OCTN1, in the liver after 1 and 28 days administration, and found that OCTN1 expression was reduced after a single dose of ET++ (Fig. 4k)
Summary
L-ergothioneine (2-mercaptohistidine trimethylbetaine, C9H15N3O2S; ET) was discovered by Charles Tanret in the ergot fungus Claviceps purpurea[1]. Despite the inability to biosynthesise ET, various animal and human tissues have been shown to accumulate ET at high concentrations[12,13,14]. This uptake of ET from dietary sources was found to be due to the transporter OCTN1 (organic cation transporter novel type-1) encoded by SLC22A414. The high retention and long turn-over could be due to renal reabsorption and low urinary excretion[13] Even with such avid retention and nearly ubiquitous distribution throughout the body, there are no reports of symptoms due to ET deficiency, some studies have demonstrated a predisposition to stress[12]. Hercynine and S-methyl ET have been detected in human blood and urine, with high correlation to ET concentrations in the body[13,41]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call