Topically applied melatonin ameliorates radiation-induced skin fibrosis in mice
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D.H. Kim , Y.M. Choi , Y.K. Ki , K.S. Cho , Y.J. Choi , W.T. Kim |
Department of Radiation Oncology, Otorhinolaryngology, and Hemato-oncology, Biomedical Research Institute, Pusan National University Hospital and Pusan National University School of Medicine, Pusan National University, Busan, Korea , rokwt@hanmail.net |
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Abstract: (2846 Views) |
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. |
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Keywords: Melatonin, Radiation, Fibrosis, Transforming growth factor-β, Topical application. |
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Full-Text [PDF 1906 kb]
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Type of Study: Original Research |
Subject:
Radiation Biology
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