tretinoin and retinyl-retinoate

  Retinoids have been used for the treatment of skin disorders such as acne, psoriasis, and photoaging. However, despite their beneficial effects, topical retinoids often cause severe local irritation called retinoid dermatitis. We previously developed a novel vitamin A derivative, retinyl retinoate, which induces less irritation and affords excellent tolerance. In this study, we examined whether co-treatment with topical peroxisome proliferator-activated receptor-α (PPARα) agonists (e.g. WY14643) reduce retinoid dermatitis in hairless mouse skin..   The effect of concomitant treatment with a PPARα agonist on retinoid dermatitis in hairless mouse epidermis was evaluated by measuring transepidermal water loss, epidermal histology, and cytokine expression..   Retinyl retinoate induced less severe retinoid dermatitis than retinoic acid. Topical application of a PPARα agonist improved the stratum corneum structure and function, reduced mRNA expression of interleukin (IL)-1α, tumor necrosis factor-α and IL-8, and inhibited ear edema induced by retinoic acid or retinyl retinoate..   Our results indicate that PPARα agonists can potentially be used to improve retinoid dermatitis. We suggest that co-treatment with retinyl retinoate and a PPARα agonist may reduce or prevent detrimental alterations in retinoid-treated skin.

Topics: Administration, Topical; Animals; Cell Differentiation; Cell Proliferation; Dermatitis; Enzyme Inhibitors; Epidermis; Female; Interleukin-1alpha; Interleukin-8; Keratolytic Agents; Liver X Receptors; Mice; Mice, Hairless; Orphan Nuclear Receptors; Palmitic Acid; PPAR alpha; Pyrimidines; Retinoids; Retinyl Esters; RNA, Messenger; Tretinoin; Tumor Necrosis Factor-alpha; Water Loss, Insensible

A new hybrid, retinyl retinoate 1, was synthesized with a condensing reaction between retinol and retinoic acid to improve the photo-stability, and the in vitro biological activity of the hybrid was analyzed. This retinol derivative had enhanced thermal stability and decreased photosensitivity, and exhibited decreased cell toxicity compared to that of retinol. In addition, RAR activity analysis showed that retinyl retinoate 1 had higher inhibitory activity against c-Jun than retinol and showed superior effects on collagen synthesis compared to retinol. Thus, retinyl retinoate 1 may have the potential to be conveniently used as an additive in cosmetics for prevention and improvement of skin aging and medicines for the treatment of skin troubles due to its excellent stability under severe and accelerated conditions.

Topics: Cells, Cultured; Collagen; Humans; Light; Receptors, Retinoic Acid; Retinoids; Retinyl Esters; RNA, Messenger; Skin Aging; Transcription Factor AP-1; Tretinoin; Vitamin A