A major research topic consists of revealing the contribution of radical-mediated reactions in dermatological diseases related to xenobiotic-induced stress to succeed risk-assessment procedures protecting producers and consumers. Allergic contact dermatitis is the clinically relevant consequence of skin sensitization, one of the most critical occupational and environmental health issues related to xenobiotics exposure. The first key event identified for the skin sensitization process to a chemical is its aptitude to react with epidermal proteins and form antigenic structures that will further trigger the immune response. Many chemical sensitizers are suspected to react through mechanisms involving radical intermediates. This review focuses on the recent progress we have accomplished over the last few years studying radical intermediates derived from skin-sensitizing chemicals by electron paramagnetic resonance in combination with the spin-trapping technique. Our work is carried out "from the molecule", performing studies in solution, "to the tissue", by the development of a methodology on a reconstructed human epidermis model, very close in terms of histology and metabolic/enzymatic activity to real human epidermis, that can be used as suitable biological tissue model. The benefits are to test chemicals under conditions close to human use and real-life sensitization exposures and benefit from the three-dimensional (3D) microenvironment.
Keywords: allergic contact dermatitis; electron paramagnetic resonance; endoperoxides; hydroperoxides; radical mechanisms; reconstructed human epidermis.
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