Topically applied melatonin ameliorates radiationinduced skin fibrosis in mice

Background: we investigated whether topical administration of melatonin ameliorates radiation-induced skin fibrosis (risf) and inhibits the expression of profibrogenic genes in mice. materials and methods: forty-eight female balb/c mice were randomly divided into three groups: topically applied 5% ethanol (control), topically applied 5% ethanol plus irradiation (ir), and topically applied melatonin plus irradiation (mel+ir). the right hind legs of the ir and mel+ir group mice were exposed to two fractions of electron beam radiation (20 gy × 2). for 4 weeks, melatonin solution (10 mg/day) was topically applied to mel+ir group mice. fourteen days after ir, the relative levels of transforming growth factor (tgf)-β1 mrna expression and tgf-β1 protein in skin specimens were analyzed by real-time quantitative pcr and immunohistochemical staining. dermal thickness and tissue collagen accumulation were measured at 100 days post irradiation. results: the radiation caused a 2.2-fold increase in tgf-β1 mrna expression relative to that in control group, which was decreased by 37% following melatonin treatment (p = 0.024). we also observed substantial reduction of tgf-β1 expression in immunohistochemical studies. the mean values of dermal thickness were 105 ± 11 μm (control), 195 ± 21 μm (ir), and 148 ± 19 μm (mel+ir). dermal thickness and collagen accumulation, which increased in the ir group, was significantly reduced by topically applied melatonin. conclusion: topical administration of melatonin successfully attenuated risf.