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Oral glutathione administration results in a lightening of skin color in a small number of subjects. However, long-term safety has not been established and warrants more extensive clinical trials.

Tyrosinase, the rate-limiting enzyme for melanin synthesis, is induced after ultraviolet irradiation as part of the tanning response, the major recognized photoprotective response of human skin. Other DNA-damaging agents and DNA fragments such as thymidine dinucleotides also induce tyrosinase gene expression. Moreover, like ultraviolet light they also activate p53. To determine whether p53 activation is required for this increased tyrosinase expression, we employed two experimental systems: (i) a human melanoma line (WM35) known to express wild-type p53 versus WM35 cells engineered to express a transcriptionally inactive dominant-negative p53 (WM35-p53DN) or the empty vector alone (WM35-pCMV7) and (ii) mice with wild-type p53 versus p53 knockout mice. In WM35-p53DN cells, the baseline p53 protein level was higher than in WM35 or WM35-pCMV7 cells, and tyrosinase transcripts were lower. After ultraviolet irradiation, in all cell lines the p53 protein level increased within the first 24 h, as expected; and at 24 h tyrosinase mRNA levels were decreased. Consistent with the literature, these data in combination suggest that increased p53 protein level downregulates tyrosinase mRNA. In WM35 and WM35-pCMV7 cells at 48 and 72 h, however, whereas p53 levels remained elevated, tyrosinase mRNA levels compared to pre-irradiation levels tripled, whereas in WM35-p53DN cells levels remained below baseline. In thymidine-dinucleotide-treated WM35 and WM35-pCMV7 cells there was a comparable upregulation of tyrosinase mRNA within 24 h that persisted through 72 h, but there was no upregulation of tyrosinase mRNA in WM35-p53DN cells any time after ultraviolet irradiation or thymidine dinucleotide treatment. In ear skin of p53 wild-type mice, topical application of thymidine dinucleotide induced a 4-5-fold increase in epidermal melanin content after 3 wk, but in p53 knockout mice thymidine dinucleotide application caused no detectable increase in melanin. Together, these data demonstrate that p53 activation increases tyrosinase mRNA level and subsequently pigmentation. The data further suggest that tanning is part of a p53-mediated adaptive response of mammalian skin to DNA damage from ultraviolet irradiation.

BackgroundPrevious studies showed that supplementation of reduced form of glutathione (GSH, 500 mg/d) has a skin-lightening efficacy in humans. This study was designed to evaluate the influences of both GSH and oxidized form (GSSG), at doses lower than 500 mg/d, on improving skin properties.Patients and methodsA randomized, double-blind, placebo-controlled, parallel, three-arm study was conducted. Healthy female subjects were equally randomized into three groups and took GSH (250 mg/d), GSSG (250 mg/d), or placebo orally for 12 weeks. At each visit at baseline and for 12 weeks, skin features including melanin index, wrinkles, and other relevant biophysical properties were measured. Blood samples were collected for safety monitoring.ResultsIn generalized estimating equation analyses, melanin index and ultraviolet spots of all sites including face and arm when given GSH and GSSG tended to be lower than placebo. At some sites evaluated, subjects who received GSH showed a significant reduction in wrinkles compared with those taking placebo. A tendency toward increased skin elasticity was observed in GSH and GSSG compared with placebo. There were no serious adverse effects throughout the study.ConclusionWe showed that oral glutathione, 250 mg/d, in both reduced and oxidized forms effectively influences skin properties. Overall, glutathione in both forms are well tolerated.

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Targeted narrowband UVB phototherapy plus topical tetrahydrocurcuminoid cream was slightly more effective than targeted narrowband UVB monotherapy for vitiligo located in UV-sensitive areas. However, the differences in degrees of repigmentation did not reach statistically significant levels.

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