Ergothioneine, an adaptive antioxidant for the protection of injured tissues? A hypothesis

Ergothioneine (ET) is a diet-derived, thiolated derivative of histidine with antioxidant properties. Although ET is produced only by certain fungi and bacteria, it can be found at high concentrations in certain human and animal tissues and is absorbed through a specific, high affinity transporter (OCTN1). In liver, heart, joint and intestinal injury, elevated ET concentrations have been observed in injured tissues. The physiological role of ET remains unclear. We thus review current literature to generate a specific hypothesis: that the accumulation of ET in vivo is an adaptive mechanism, involving the regulated uptake and concentration of an exogenous natural compound to minimize oxidative damage. •Ergothioneine (ET) is a powerful antioxidant.•It originates from fungi and bacteria but can accumulate at high levels in human tissues.•We propose that it is deliberately accumulated at sites of tissue injury in vivo as a cytoprotective mechanism.•This may be achieved by increasing the levels of OCTN1, the ergothioneine transporter.