Interaction of a functionalized complex of the flavonoid hesperetin with the AhR pathway and CYP1A1 expression: involvement in its protective effects against benzo[a]pyrene-induced oxidative stress in human skin

Abstract

Skin cancer pathogenesis is partially associated to the oxidative stress conditions induced by environmentally carcinogens such as benzo[a]pyrene (BaP). The protective effects against BaP-induced oxidative stress of the flavonoid hesperetin as a complex with the 2-hydroxypropyl-β-cyclodextrin (HE/HP-β-CyD) have been evaluated using an ex vivo human skin model. Human healthy skin has been pre-treated with the functionalized complex HE/HP-β-CyD (0.5-50 μM) before BaP (5 μM) application simulating occupational and environmental exposure. Oxidative stress was evaluated in terms of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheyltetrazolium bromide reduction, protein peroxidation and reactive oxygen species (ROS) formation. Additionally, it has been investigated whether the potential protective effects of HE/HP-β-CyD may be correlated to the interaction with aryl hydrocarbon receptor (AhR) pathway. A significant protection by HE/HP-β-CyD against the BaP-induced increase in ROS and carbonyl compound production, as well as reduction in tissue viability, has been observed (p<0.001). Results obtained showed that HE/HP-β-CyD was also able to reduce BaP-induced AhR and CYP1A1 protein expression (p<0.001). Experimental evidences provided from this study suggest significant preventive properties of HE/HP-β-CyD in the toxicity caused by environmental carcinogens such as PAHs.