Plasma Retinoids after Topical Use of Retinaldehyde on Human Skin

Sass, Jörn Oliver; Masgrau, E.; Piletta, Pierre; Nau, Heinz; Saurat, J.‐H.

doi:10.1159/000211436

Cited by 10 publications

(7 citation statements)

References 12 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data may constitute a basis for risk assessment of dermally applied (all-trans-) retinoic acid in therapy, since no increase in plasma concentration was observed by other investigators under experimental conditions [13][14][15][16]. Endogenous plasma concentrations of about 2 ng/ml (all-trans-) retinoic acid do not increase after topical administration of dermatological ointments [16].…”

Section: Discussionmentioning

confidence: 66%

Absorption and Metabolism of (all-trans-) Retinol Acetate, Retinol, and Retinoic Acid in the Single-Pass, Albumin-Perfused Rabbit Ear

Bast

Kampffmeyer

1998

Skin Pharmacol Physiol

View full text Add to dashboard Cite

Background: Retinoic acid, a metabolite of retinol, is formed in the skin of various species. Purpose: Formation rates have not been determined in a dynamic skin perfusion model which may show the dehydrogenation of retinol to be rate limited. Methods: (all-trans-) Retinol acetate, retinol, or retinoic acid was applied dermally with isopropyl myristate. The ears were single-pass perfused with 6% hetastarch or 5% bovine serum albumin in the buffer solution. The effluent was analyzed by HPLC for these substances. Result: No ester hydrolysis of retinol acetate was observed, nor did this substrate appear in the effluent. Retinol or retinoic acid were detected in the effluent. The absorption rate was linearly related to the dermally applied concentration density. The absorption rate of retinoic acid was 70 times larger than that for retinol. The formation rate of retinoic acid from retinol was rate limited (apparent V_max: 0.08 pmol/min/cm² skin). Conclusion: Since retinoic acid is a recognized pharmacologically active ingredient in the skin, the dehydrogenation of retinol or retinal was also observed in the effluent of this skin perfusion model. The percutaneous retinol adds to the endogenous pool of retinoic acid by cytosolic dehydrogenation or microsomal oxidation elsewhere. The steady-state absorption rate of 0.1% retinoic acid in isopropyl myristate, referred to 500 cm² of the human skin, would contribute about 20% of the daily requirement of vitamin A, without increase in endogenous retinoic acid plasma concentration.

show abstract

Section: Discussionmentioning

confidence: 66%

Absorption and Metabolism of (all-trans-) Retinol Acetate, Retinol, and Retinoic Acid in the Single-Pass, Albumin-Perfused Rabbit Ear

Bast

Kampffmeyer

1998

Skin Pharmacol Physiol

View full text Add to dashboard Cite

show abstract

“…1c). Such a concentration in the microenvironment of melanocytes is unlikely since melanocytes are very close to the superficial dermal blood vessels and no modulation of plasma retinoid levels can be detected following topical retinoid application [29,30], which indicates that very low retinoid concentrations may reach these blood vessels following topical application of 0.05% retinoids. However, we cannot rule out the possibility that the decreased activity of tyrosinase observed in vitro (fig.…”

Section: Discussionmentioning

confidence: 99%

The Potential Depigmenting Activity of Retinaldehyde

Sorg

Kasraee²,

Salomon³

et al. 2013

Dermatology

Self Cite

View full text Add to dashboard Cite

Background: Retinoids have been reported to exert depigmenting activity. Unlike most depigmenting agents that target tyrosinase, they are not phenolic agents and may act via different mechanisms. Objectives: We analysed the properties of retinaldehyde (RAL), a precursor of retinoic acid (RA), as a skin-lightening agent in various models. Methods: The viability and the depigmenting properties of RAL were assessed in murine melanocytes, in human reconstructed epidermis, and in mice and guinea pigs. The melanin content and cytotoxicity were assessed in melanocytes; in 3-dimensional models, the melanin concentration and the number of active melanocytes were determined. Results: RAL was taken up by melanocytes and mostly metabolised to retinol and retinyl esters, and to a lesser extent to RA. RAL decreased the melanin concentration of guinea pig ears and mouse tails by 54 and 74%, respectively, and decreased the number of active melanocytes by 42 and 77%, respectively. In reconstructed epidermis the melanin concentration was increased by 52%, whereas the number of active melanocytes decreased by 44%. Conclusion: RAL exerts a significant depigmenting activity with a mode of action that looks different from that of RA. Our data suggest a skin-lightening effect related to a melanolytic action (i.e. a decrease in melanin concentration, whatever the mechanism) rather than to melanocytotoxicity, besides other still unknown actions of RAL on melanocytes.

show abstract

“…Only severe conditions require the use of oral retinoids, in order to induce high systemic concentrations, with the problems of side effects and teratogenic properties that preclude their use for pregnant women [25]. For both cosmetic use and treatments of mild to moderate cutaneous diseases, topical application of retinoids represent a good approach to deliver retinoids directly to the skin; in such cases, systemic concentrations seem to be unaffected [26,27]. However, very few in vivo human studies examining the epidermal concentrations of retinoids following topical application were performed to date [28,29].…”

Section: Discussionmentioning

confidence: 99%

Penetration and Metabolism of Topical Retinoids in ex vivo Organ-Cultured Full-Thickness Human Skin Explants

Antille

Tran

Sorg

et al. 2004

Skin Pharmacol Physiol

Self Cite

View full text Add to dashboard Cite

The human epidermis contains endogenous retinoids [retinol (vitamin A) and retinyl esters] and carotenoids (mostly β-carotene). Previous studies in the mouse have shown that the enzymes involved in retinoid metabolism are present in the epidermis. In this study, we wanted to assess the skin penetration and metabolism of topical retinoids in the human. To do this, fresh surgically excised human abdominal skin was mounted on Franz perfusion cells. Topical retinoic acid, retinal, retinol and retinyl palmitate were applied at 2.5 mg/cm² in oil-in-water creams containing 0.05% retinoids on the donor compartment, while the receptor compartment was filled with culture medium. The skin was incubated for 24 h at 37°C, then epidermal retinoid concentrations were determined by HPLC. The same experiment was performed with mouse back skin mounted on Franz cells. Finally, topical retinoids were applied on the back of hairless mice for 24 h; then the mice were sacrificed and retinoid concentrations were assayed in the epidermis. In all three models, retinol and its esters were found to be endogenous, as was the case in previous studies in the mouse in vivo. The four applied retinoids penetrated well into the epidermis. Topical retinoic acid did not increase endogenous retinoids, whereas the latter were greatly increased following topical retinal in the mouse. Retinal was also metabolized into retinoic acid, unlike topical retinol and retinyl palmitate, which only increased endogenous retinoids. Topical retinal and retinol did undergo a higher metabolism in both mouse models than in human skin. In summary, the penetration and metabolism patterns of topical retinoids were quite similar in the two mouse models used, indicating that the Franz cells appear to be a good model to predict in vivo metabolism of topical retinoids. When applying this concept to our results obtained in Franz cells with human skin, we conclude that topical retinol and retinal load human skin with both storage and functional vitamin A.

show abstract

Plasma Retinoids after Topical Use of Retinaldehyde on Human Skin

Cited by 10 publications

References 12 publications

Absorption and Metabolism of (all-trans-) Retinol Acetate, Retinol, and Retinoic Acid in the Single-Pass, Albumin-Perfused Rabbit Ear

Absorption and Metabolism of (all-trans-) Retinol Acetate, Retinol, and Retinoic Acid in the Single-Pass, Albumin-Perfused Rabbit Ear

The Potential Depigmenting Activity of Retinaldehyde

Penetration and Metabolism of Topical Retinoids in ex vivo Organ-Cultured Full-Thickness Human Skin Explants

Contact Info

Product

Resources

About