In Situ Metabolism of Cinnamyl Alcohol in Reconstructed Human Epidermis: New Insights into the Activation of This Fragrance Skin Sensitizer.
Chemical modification of epidermal proteins by skin sensitizers is the molecular event which initiates the induction of contact allergy. However, not all chemical skin allergens react directly as haptens with epidermal proteins but need either a chemical (prehaptens) or metabolic (prohaptens) activation step to become reactive. Cinnamyl alcohol has been considered a model prohapten, as this skin sensitizer has no intrinsic reactivity. Therefore, the prevailing theory is that cinnamyl alcohol is enzymatically oxidized into the protein-reactive cinnamaldehyde, which is the sensitizing agent. Knowing that reconstructed human epidermis (RHE) models have been demonstrated to be quite similar to the normal human epidermis in terms of metabolic enzymes, use of RHE may be useful to investigate the in situ metabolism/activation of cinnamyl alcohol, particularly when coupled with high-resolution magic angle spinning nuclear magnetic resonance. Incubation of carbon-13 substituted cinnamyl derivatives with RHE did not result in the formation of cinnamaldehyde. The metabolites formed suggest the formation of an epoxy-alcohol and an allylic sulfate as potential electrophiles. These data suggest that cinnamyl alcohol is inducing skin sensitization through a route independent of the one involving cinnamaldehyde and should therefore be considered as a skin sensitizer on its own.
Institute of Chemistry, CNRS UMR 7177 and University of Strasbourg , 4 Rue Blaise Pascal, 67081 Strasbourg, France.
Eric
E
Moss
Institute of Chemistry, CNRS UMR 7177 and University of Strasbourg , 4 Rue Blaise Pascal, 67081 Strasbourg, France.
Camille
C
Debeuckelaere
Institute of Chemistry, CNRS UMR 7177 and University of Strasbourg , 4 Rue Blaise Pascal, 67081 Strasbourg, France.
Valérie
V
Berl
Institute of Chemistry, CNRS UMR 7177 and University of Strasbourg , 4 Rue Blaise Pascal, 67081 Strasbourg, France.|Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), CNRS UMR 7357 and University of Strasbourg , 4 Rue Blaise Pascal, 67081 Strasbourg, France.
Karim
K
Elbayed
Institute of Chemistry, CNRS UMR 7177 and University of Strasbourg , 4 Rue Blaise Pascal, 67081 Strasbourg, France.|Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), CNRS UMR 7357 and University of Strasbourg , 4 Rue Blaise Pascal, 67081 Strasbourg, France.
François-Marie
FM
Moussallieh
Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), CNRS UMR 7357 and University of Strasbourg , 4 Rue Blaise Pascal, 67081 Strasbourg, France.
Izzie-Jacques
IJ
Namer
Institute of Chemistry, CNRS UMR 7177 and University of Strasbourg , 4 Rue Blaise Pascal, 67081 Strasbourg, France.
J-P
JP
Lepoittevin
D066241:Carbon-13 Magnetic Resonance Spectroscopy; D006801:Humans; D020005:Propanols / Q000378:metabolism* / Q000494:pharmacology; D066244:Proton Magnetic Resonance Spectroscopy; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
D020005:Propanols; C020722:cinnamyl alcohol