Ergothioneine produces relaxation in isolated rat aorta by inactivating superoxide anion

G. Gokce, M.Z. Arun

Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey. goksel.gokce@ege.edu.tr

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• Pharmacology

OBJECTIVE: Ergothioneine (EGT) is a ubiquitous, sulphur-containing derivative of amino acid histidine, acquired by higher order plants and animals solely through dietary means. The antioxidant and cytoprotective effects of ergothioneine have been demonstrated by in vitro studies, but its physiological role remains unclear. This study aims to investigate the effects of ergothioneine (EGT) on basal and acetylcholine-stimulated activity of nitric oxide.

MATERIALS AND METHODS: Effects of EGT on basal and acetylcholine (ACh)-stimulated activity of nitric oxide (NO) were tested in isolated rings of rat thoracic aorta. In parallel experiments, relaxant responses to ACh were evaluated following incubation with Cu/Zn superoxide dismutase inhibitor diethyldithiocarbamate (DETCA) and superoxide anion generating system hypoxanthine/xanthine oxidase (HX/XO). Generation of reactive oxygen species (ROS) in aortic rings was measured by means of lucigenin- and luminol-enhanced chemiluminescence, in the presence and in the absence of EGT.

RESULTS: EGT (1-200 µM) produced a concentration-dependent relaxation in endothelium-intact aortic rings which was abolished by endothelial denudation or NO synthase inhibition. Impaired response to ACh in DETCA and HX/XO treated rings was recovered by EGT treatment. This recovery by EGT was characterized by a significant decrease in the production of superoxide anion.

CONCLUSIONS: Ergothioneine, at levels normally present in blood, may protect NO from destruction by superoxide anion and play a physiologically important role in preserving NO-dependent endothelial function.

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