Biological activities of topical retinaldehyde

Background: We had hypothesised that retinaldehyde (RAL) should be an inter esting precursor for topical use. Aim: We review our observations about its biological activities. Methods: We performed pilot studies to explore its biological effects and tolerability in human skin and compared the effects of topical RAL to that of all-trans-retinoic acid (RA) in the mouse tail te st. Results: The biological activities of RAL were found to be qualitativel y identical to that of RA: (i) induction of cellular RA-binding protein typ e 2 mRNA and protein, (ii) increase in epidermal proliferation (increase in DNA synthesis, epidermal thickness, induction of 50-kD keratin mRNA and re duction in 70-kD keratin mRNA), and (iii) metaplastic effects (induction of orthokeratosis, reduction of 65-kD keratin mRNA, increase in filaggrin and loricrin mRNAs). When associated with RAL, citral (known for its capacity to inhibit the oxidation of retinol to RA in epidermis) counteracted the ef fects induced by RAL indicating that RAL exerts biological activities throu gh transformation to RA. Hypothesising that keratinocytes would metabolize 9-cis-RAL to 9-cis-RA, we compared the biological effects induced by topica l 9-cis-RAL and found that hyperplastic and metaplastic responses were lowe r than those induced by all-trans-RAL or all-trans-RA at similar concentrat ions. This suggests that 9-cis-RAL has no advantage over all-trans-RAL for specific delivery of natural retinoids into the skin. As in clinical studie s conducted in human skin, we also found topical RAL less irritant than RA. Conclusion: These studies indicate that topical RAL has biological activit y and is well tolerated.