Resveratrol has antagonist activity on the aryl hydrocarbon receptor: Implications for prevention of dioxin toxicity

Aryl hydrocarbon receptor (AhR) ligands such as dioxin and benzo[a] pyrene are environmental contaminants with many adverse health effects, including immunosuppression, carcinogenesis, and endothelial cell damage. We show her e that a wine component, resveratrol (3,5,4'-trihydroxystilbene), is a comp etitive antagonist of dioxin and other AhR ligands. Resveratrol promotes Ah R translocation to the nucleus and binding to DNA at dioxin-responsive elem ents but subsequent transactivation does not take place. Resveratrol inhibi ts the transactivation of several dioxin-inducible genes including cytochro me P-450 1A1 and interleukin-1 beta, both ex vivo and in vivo. Resveratrol has adequate potency and nontoxicity to warrant clinical testing as a proph ylactic agent against aryl hydrocarbon-induced pathology.