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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.

High Glucose Enhances Skin Sensitizer-induced NRF2 Activation In Vitro