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

Masutaka Furue; Yoko Fuyuno; Chikage Mitoma; Hiroshi Uchi; Gaku Tsuji

doi:10.3390/antiox7070090

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

Antioxidants (Basel). 2018 Jul 13;7(7):90. doi: 10.3390/antiox7070090.

Authors

Masutaka Furue^{1

2

3}, Yoko Fuyuno^{4

5}, Chikage Mitoma^{6

7}, Hiroshi Uchi⁸, Gaku Tsuji⁹

Affiliations

¹ Department of Dermatology, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka 812-8582, Japan. furue@dermatol.med.kyushu-u.ac.jp.
² Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka 812-8582, Japan. furue@dermatol.med.kyushu-u.ac.jp.
³ Division of Skin Surface Sensing, Kyushu University, Fukuoka 812-8582, Japan. furue@dermatol.med.kyushu-u.ac.jp.
⁴ Department of Dermatology, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka 812-8582, Japan. y-kuba@dermatol.med.kyushu-u.ac.jp.
⁵ Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka 812-8582, Japan. y-kuba@dermatol.med.kyushu-u.ac.jp.
⁶ Department of Dermatology, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka 812-8582, Japan. mchikage@dermatol.med.kyushu-u.ac.jp.
⁷ Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka 812-8582, Japan. mchikage@dermatol.med.kyushu-u.ac.jp.
⁸ Department of Dermatology, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka 812-8582, Japan. uchihir@dermatol.med.kyushu-u.ac.jp.
⁹ Department of Dermatology, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka 812-8582, Japan. gakku@dermatol.med.kyushu-u.ac.jp.

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.

Keywords: Yusho; aryl hydrocarbon receptor; chloracne; dioxin; heme oxygenase-1; nuclear factor-erythroid 2-related factor-2.

Publication types

Review