Co‐treatment with retinyl retinoate and a PPARα agonist reduces retinoid dermatitis

Abstract Background 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. Methods 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. Results 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. Conclusions 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.