Metabolism of topical retinaldehyde.

Objective: In order to circumvent the tolerance problems encountered with topical application of retinoic acid - a biologically active metabolite of vitamin A - we performed in various models a series of experiments aimed at assessing the bio-availability of topical retinaldehyde and its conversion into either retinoid stores or biologically active metabolites.

Methods: (i) (3)H-retinaldehyde was used as a precursor of either (3)H-retinol or (3)H-retinoic acid in human skin extracts and human cultured keratinocytes; (ii) the concentration of various retinoids resulting from the metabolism of topical retinaldehyde was determined in mouse skin and in human plasma. Retinoids were quantified by reverse-phase HPLC with UV detection.

Results: Human keratinocytes were shown to take up retinaldehyde and to convert it into retinoic acid in a differentiation-dependent manner, differentiating cells oxidising retinaldehyde more efficiently. In vivo models allowed us to demonstrate that retinaldehyde is taken up by the skin and is then predominantly converted into retinyl esters - a storage form of vitamin A - while delivering relatively low amounts of retinoic acid from a large reservoir.

Conclusion: Topical retinaldehyde can be used as a precursor of endogenous retinoids, since it is converted into both storage and bio-active forms of vitamin A.