Efficacy of 0.1% adapalene in a non-inflammatory Kyoto Rhino Rat acne model.

Abstract

BACKGROUND: Acne vulgaris is a disorder of the pilosebaceous unit of the skin, and the underlying mechanism is still obscure. Kyoto rhino (krh/krh) rats were made by ethylnitrosourea (ENU) mutagenesis and harbor S413X nonsense mutation of the rat hairless (Hr) gene. Krh/krh rats develop comedones with hair loss on their back as they grow. OBJECTIVE: Our purpose is to assess whether or not the krh/krh rat is a suitable model of non-inflammatory acne, and to investigate the comedolytic effects of adapalene in krh/krh rats. METHODS: Krh/krh rats at 12weeks of age were topically treated with adapalene or a vehicle 6 times a week, for 12weeks. Skin lesions were clinically investigated and skin samples were obtained from treated skins from each animal after 6 and 12weeks of treatments. RESULTS: Comedone was clinically enlarged in the control group compared with the adapalene group. The adapalene group showed significantly increased epidermal thickness as compared to the control group. Furthermore, open comedone areas were also significantly decreased in the adapalene group as compared to the control group. The adapalene group also showed reduced lipid production in open comedones as compared to the control group. Cytokine productions including IL-10 and IL-12a tended to increase in skin treated with adapalene as compared to the control group. CONCLUSION: Krh/krh rats represented a new model for non-inflammatory acne with abnormalities in both hair follicles and sebaceous glands. It is hypothesized that adapalene is a superior drug to decrease open comedones by modifying lipid metaboism and cytokine production in krh/krh rats.