Metabolism of topical retinaldehyde

Objective: In order to circumvent the tolerance problems encountered with t opical application of retinoic acid - a biologically active metabolite of v itamin 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 ) H-3-retinaldehyde was used as a precursor of either H-3-retinol or H-3-re tinoic acid in human skin extracts and human cultured keratinocytes; (ii) t he concentration of various retinoids resulting from the metabolism of topi cal retinaldehyde was determined in mouse skin and in human plasma. Retinoi ds were quantified by reverse-phase HPLC with UV detection. Results: Human keratinocytes were shown to take up retinaldehyde and to convert it into re tinoic acid in a differentiation-dependent manner, differentiating cells ox idising retinaldehyde more efficiently. In vivo models allowed us to demons trate that retinaldehyde is taken up by the skin and is then predominantly converted into retinyl esters - a storage form of vitamin A - while deliver ing relatively low amounts of retinoic acid from a large reservoir. Conclus ion: Topical retinaldehyde can be used as a precursor of endogenous retinoi ds, since it is converted into both storage and bioactive forms of vitamin A.