title: Metabolism of topical retinaldehyde and retinol by mouse skin in vivo: predominant formation of retinyl esters and identification of 14-hydroxy-4, 14-retro-retinol.
abstract: We have previously shown that retinaldehyde (RAL), a natural metabolite of beta-carotene and retinol (ROL), can be used topically in human skin and exerts biological activity; it may be a convenient way to deliver multipotential vitamin A activity in epidermis. RAL can be converted enzymatically into 2 pathways: one leads to ROL (and then retinyl esters), the other to retinoic acid (RA). The aim of the present study was 2-fold: (i) to see if RAL is metabolised in vivo when topically applied on mouse skin, and (ii) if so, to analyse the occurrence and relative importance of the 2 metabolic pathways as compared to ROL. We studied by HPLC the metabolites detectable in mouse tail skin upon topical application of RAL and ROL. As compared to vehicle-treated controls, RAL-treated mouse skin contained low amounts of all-trans RA and 13-cis-RA, whereas ROL content increased 10-fold and retinyl esters 30-fold after RAL application. As compared to RAL, ROL-treated mouse skin showed no detectable RA, slightly less retinyl esters but a significant amount of 14-hydroxy-4, 14-retro-ROL (14-HRR), a metabolite not previously reported in the skin. 14-HRR was the predominant polar metabolite of ROL. These data indicate that keratinocytes metabolise topical RAL, thus confirming the concept of using RAL as a precursor. Both pathways are used but in significantly different proportions. Thus, only a low proportion of RAL is metabolised into all-trans-RA, which may explain the low irritancy profile of topical RAL and supports the concept of a controlled delivery of ligands. That keratinocytes predominantly channel RAL into storage forms indicates that RAL should also be considered as a convenient way to load the epidermis with vitamin A. The detection of 14-HRR, a metabolite not previously reported in skin, that promotes growth of B Iymphocytes and activation of T Iymphocytes, suggests distinct potentials of topical ROL and RAL.
authors.affiliation: Department of Dermatology, University Hospital, Geneva, Switzerland.
authors.forename: J O
authors.initials: JO
authors.lastname: Sass
authors.forename: L
authors.initials: L
authors.lastname: Didierjean
authors.forename: P
authors.initials: P
authors.lastname: Carraux
authors.forename: C
authors.initials: C
authors.lastname: Plum
authors.forename: H
authors.initials: H
authors.lastname: Nau
authors.forename: J H
authors.initials: JH
authors.lastname: Saurat
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes; D004952:Esters / Q000378:metabolism; D015603:Keratinocytes / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012172:Retinaldehyde / Q000378:metabolism*; D012176:Retinoids / Q000032:analysis*; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D004224:Diterpenes; D004952:Esters; D012176:Retinoids; D014801:Vitamin A; C072014:14-hydroxy-4,14-retro-retinol; D012172:Retinaldehyde