Scientific article

Metabolism and biological activities of topical 4-oxoretinoids in mouse skin

Published inJournal of investigative dermatology, vol. 128, no. 4, p. 999-1008
Publication date2008

Retinoic acid mediates most of the biological actions of vitamin A. It is oxidized by CYP26A1 to 4-oxoretinoic acid, considered as an inactive catabolite of retinoic acid. However, in the light of studies reporting the presence of 4-oxoretinal or 4-oxoretinol as the predominant retinoids during morphogenesis, we analyzed the retinoid-like biological activity of these oxoretinoids in mouse skin in vivo. Topical 4-oxoretinal and 4-oxoretinol promoted significant epidermal hyperplasia and metaplasia in mouse tail. They induced a moderate response for epidermal inflammation, compared with retinal, whereas neither 4-oxoretinal nor 4-oxoretinol prevented menadione-induced epidermal lipid peroxidation, unlike retinal and retinol. As analyzed by quantitative PCR, 4-oxoretinal and 4-oxoretinol did not reproduce the significant increased expression of genes coding for keratin 4, amphiregulin, heparin-EGF and CYP26A1, that did induce retinal and retinol. However, both retinal and 4-oxoretinal significantly inhibited the lipopolysaccharide-induced maturation of human dendritic cells in vitro. As analyzed in vivo and in vitro, 4-oxoretinal and 4-oxoretinol were not converted into retinoic acid. We conclude that 4-oxoretinal and 4-oxoretinol exert a moderate direct retinoid-like activity in vivo, thus confirming previous in vitro studies in amphibians showing 4-oxometabolites of vitamin A as bioactive agents rather than inactive catabolites.

  • Animals
  • Dendritic Cells/drug effects/metabolism
  • Epidermis/drug effects/metabolism/pathology
  • Gene Expression/drug effects
  • Humans
  • Hyperplasia/chemically induced
  • Lipid Peroxidation/drug effects
  • Mice
  • Peroxidase/metabolism
  • Retinaldehyde/analogs & derivatives/chemistry/metabolism/pharmacology
  • Retinoids/pharmacology
  • Skin/drug effects/metabolism/pathology
  • Tail
  • Vitamin A/analogs & derivatives/chemistry/metabolism/pharmacology
Citation (ISO format)
SORG, Olivier et al. Metabolism and biological activities of topical 4-oxoretinoids in mouse skin. In: Journal of investigative dermatology, 2008, vol. 128, n° 4, p. 999–1008. doi: 10.1038/sj.jid.5701106
Main files (1)
Article (Accepted version)
ISSN of the journal0022-202X

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