Potential of EPR spin-trapping to investigate in situ free radicals generation from skin allergens in reconstructed human epidermis: cumene hydroperoxide as proof of concept

The first step in the development of skin sensitisation to a chemical, and in the elicitation offurther allergic contact dermatitis (ACD), is the binding of the allergen to skin proteins after pene-trating into the epidermis. The so-formed antigenic adduct is then recognised by the immunesystem as foreign to the body. Sensitising organic hydroperoxides derived from autoxidation ofnatural terpenes are believed to form antigens through radical-mediated mechanisms, althoughthis has not yet been established. So far,in vitroinvestigations on reactive radical intermediatesderived from these skin sensitisers have been conducted in solution, yet with experimental condi-tions being far away from real-life sensitisation. Herein, we report for the first time, the potentialuse of EPR spin-trapping to study thein situgeneration of free radicals derived from cumenehydroperoxide CumOOH in a 3D reconstructed human epidermis (RHE) model, thus much closerto what may happenin vivo. Among the undesirable effects associated with dermal exposure toCumOOH, it is described to cause allergic and irritant dermatitis, being reported as a significantsensitiser. We considered exploiting the usage of spin-trap DEPMPO as an extensive view of allsort of radicals derived from CumOOH were observed all at once in solution. We showed that inthe EpiskinTMRHE model, both by incubating in the assay medium and by topical application,carbon radicals are mainly formed by redox reactions suggesting the key role of CumOOH-derived carbon radicals in the antigen formation process

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

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Formation of free radicals from the skin sensitizer ascaridole in a 3D epidermis model and activation of the innate immune response.

International audienc

Formation of radicals from endoperoxide ascaridole in a 3D epidermis model and activation of the innate immune response. 77th Annual Meeting of the Society of Investigative Dermatology, Chicago, États-Unis

International audienc

Understanding the skin sensitization capacity of oxidized fragrances: study in an epidermal skin environment. 77th Annual Meeting of the Society of Investigative Dermatology, Chicago, États-Unis

International audienc

Formation of free radicals from the skin sensitizer ascaridole in a 3D epidermis model and activation of the innate immune response. IUTOX (International Union of Toxicology) 15th International Congress of Toxicology. Honolulu, Hawaii, États-Unis (15-18 juillet 2019).

International audienc