Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Potential Role of NRF2 Agonist in Managing AHR-Mediated Chloracne by Dioxin

Version 1 : Received: 13 June 2018 / Approved: 13 June 2018 / Online: 13 June 2018 (10:29:35 CEST)

A peer-reviewed article of this Preprint also exists.

Furue, M.; Fuyuno, Y.; Mitoma, C.; Uchi, H.; Tsuji, G. Therapeutic Agents with AHR Inhibiting and NRF2 Activating Activity for Managing Chloracne. Antioxidants 2018, 7, 90. Furue, M.; Fuyuno, Y.; Mitoma, C.; Uchi, H.; Tsuji, G. Therapeutic Agents with AHR Inhibiting and NRF2 Activating Activity for Managing Chloracne. Antioxidants 2018, 7, 90.

Abstract

Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)–cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch inducing expression of various antioxidative enzymes such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR–CYP1A1 signaling and activates the NRF2–antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR–CYP1A1 inhibition and NRF2 activation may be useful in managing dioxin-related health hazards.

Keywords

Aryl hydrocarbon receptor; Chloracne; Dioxin; Nuclear factor-erythroid 2-related factor-2; heme oxygenase-1; Yusho

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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