The Open Toxicology Journal

2021, 7 : 8-17
Published online 2021 April 19. DOI: 10.2174/1874340402107010008
Publisher ID: TOTOXIJ-7-8

RESEARCH ARTICLE
High Glucose Enhances Skin Sensitizer-induced NRF2 Activation

Takeo Takeda1 , Masahiro Ogawa1, * , Junya Kitamoto1 , Takahiro Kyoya1 and Megumi Terada1

*Address correspondence to this author at the Life Science Research Institute, Kumiai Chemical Industry Co. Ltd., Shizuoka, Japan; Tel: +81-537-35-3160; Fax: +81-537-36-3718; E-mail: m-ogawa@kumiai-chem.co.jp

ABSTRACT

Background:

Hyperglycemia has a potentially critical role in the promotion of sensitization, however, the clear mechanism of this phenomenon is unknown. The activation of NRF2 is a key event triggered by skin sensitizers. Therefore, we investigated the effects of high glucose on the activation of NRF2 by the skin sensitizers in vitro.

Methods:

The involvement of glucose levels in NRF2 activation by cinnamaldehyde, a skin sensitizer, was assessed in human MCF-7 breast cancer cells under normal glucose conditions (1.0 g/L D-glucose) and high glucose conditions (4.5 g/L D-glucose).

Results:

High glucose induced the NRF2 transactivation, HMOX1 mRNA expression, and SOD-like activity. Nuclear NRF2 level was increased under high glucose conditions compared to normal glucose conditions. High glucose also enhanced the cinnamaldehyde-induced HMOX1 mRNA expression and SOD-like activity.

Conclusion:

Oxidative stress caused by hyperglycemia induced additionally the activation of NRF2 signaling by skin sensitizers.

Keywords:

Glucose, Skin sensitizer, Cinnamaldehyde, Oxidative stress, KEAP1-NRF2 signaling, ROS.