Therapeutic Agents with AHR Inhibiting and NRF2 Activating Activity for Managing Chloracne.

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 that induces the 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 for managing dioxin-related health hazards.

• Authors: Masutaka Furue, Yoko Fuyuno, Chikage Mitoma, Hiroshi Uchi, Gaku Tsuji
• Journal: Antioxidants (Basel, Switzerland) (Antioxidants (Basel)) Vol. 7 Issue 7 (Jul 13 2018) ISSN: 2076-3921 [Print] Switzerland
• PMID: 30011787 (Publication Type: Journal Article, Review)