Unveiling and Benefits of Topically Applied l-(+)-Ergothioneine in Periwound Region

Oxidative stress significantly impairs wound healing by prolonging inflammation and damaging surrounding tissue. l-(+)-Ergothioneine (EGT), a naturally occurring thione–thiol antioxidant transported by OCTN1, exhibits potent cytoprotective and anti-inflammatory properties. The aim of the study was to investigate whether EGT applied topically to the periwound region can accelerate healing via transdermal antioxidant action. Full-thickness excisional wounds were created on the dorsum of Wistar rats. Animals were divided into three groups: the untreated rats (control), the rats treated with EGT at concentrations of 130 or 650 μg/cm2 applied on gauze positioned in the periwound region. Wound areas were measured over 15 days. Healing kinetics were analyzed using Logistic and Weibull models. The results showed that in the EGT-treated groups wound closures accelerated compared with controls. The Logistic model predicted ~ 70% healing in controls vs. > 90% in EGT-treated animals by day 15. The 130 μg/cm2 dose of EGT achieved near-maximal efficacy, while its higher loading had no substantial additional benefit. Topically applied EGT in the periwound region significantly enhances healing, supporting its role as a transdermally active antioxidant and a promising strategy for advanced wound care.