Effects of the aminophenol analogue p-Dodecylaminophenol on mouse skin.

p-Dodecylaminophenol (p-DDAP) was designed on the basis of structure-activity relationship studies on N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR), a synthetic derivative of retinoic acid (RA). p-DDAP exhibits antioxidative activities greater than those of RA and 4-HPR. RA shows biological effects in epidermal cells that include the inhibition of differentiation to the squamous phenotype. In the current study, we examined the effects of topical p-DDAP treatment on the skin of hairless mice as compared with those of RA treatment. p-DDAP caused an increase in epidermal thickness and decreased matrix metalloprotease and hyaluronidase activities in mouse skin tissues to the same extent that RA did. p-DDAP did not induce desquamation, erythema, or inflammatory cytokine expression as observed with RA treatment. Two-dimensional polyacrylamide gel electrophoresis patterns of proteins from skin treated with p-DDAP were distinct from those treated with RA. A protein induced by both p-DDAP and RA was identified as cytokeratin 16. p-DDAP did not elevate transcriptional activities of RA nuclear receptors. These results suggest that p-DDAP improves skin as potently as RA without causing the desquamation and erythema that the latter does. An increase in cytokeratin 16 expression might be essential for the effects of both p-DDAP and RA in skin healing and maintenance.