title: Prolonged treatment of fair-skinned mice with topical forskolin causes persistent tanning and UV protection.
abstract: We previously reported that topical application of forskolin to the skin of fair-skinned MC1R-defective mice with epidermal melanocytes resulted in accumulation of eumelanin in the epidermis and was highly protective against UV-mediated cutaneous injury. In this report, we describe the long-term effects of chronic topical forskolin treatment in this animal model. Forskolin-induced eumelanin production persisted through 3 months of daily applications, and forskolin-induced eumelanin remained protective against UV damage as assessed by minimal erythematous dose (MED). No obvious toxic changes were noted in the skin or overall health of animals exposed to prolonged forskolin therapy. Body weights were maintained throughout the course of topical forskolin application. Topical application of forskolin was associated with an increase in the number of melanocytes in the epidermis and thickening of the epidermis due, at least in part, to an accumulation of nucleated keratinocytes. Together, these data suggest in this animal model, short-term topical regular application of forskolin promotes eumelanin induction and that over time, topical forskolin treatment is associated with persistent melanization, epidermal cell accumulation, and skin thickening.
authors.affiliation: Markey Cancer Center, Lexington, KY, USA.
authors.forename: Malinda L
authors.initials: ML
authors.lastname: Spry
authors.forename: Jillian C
authors.initials: JC
authors.lastname: Vanover
authors.forename: Timothy
authors.initials: T
authors.lastname: Scott
authors.forename: Osama
authors.initials: O
authors.lastname: Abona-Ama
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.forename: John A
authors.initials: JA
authors.lastname: D'Orazio
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D005576:Colforsin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000528:radiation effects; D008543:Melanins / Q000096:biosynthesis / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism; D012879:Skin Physiological Phenomena / Q000187:drug effects / Q000528:radiation effects; D012880:Skin Pigmentation / Q000187:drug effects* / Q000528:radiation effects*; D055108:Sunbathing; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D008543:Melanins; D011837:Radiation-Protective Agents; D044102:Receptor, Melanocortin, Type 1; C041877:eumelanin; D005576:Colforsin