Tranexamic Acid Ameliorates Skin Hyperpigmentation by Downregulating Endothelin-1 Expression in Dermal Microvascular Endothelial Cells.

BACKGROUND: Although reports suggest that tranexamic acid (TXA) has clinical benefits for melasma patients by oral, intralesional and topical treatment, the optimal route of TXA therapy and the underlying mechanism involved remain poorly defined. OBJECTIVE: To compare the skin lightening effect between oral TXA and topical TXA and to dissect the molecular mechanisms using ultraviolet B (UVB)-induced hyperpigmentation mouse model, ex vivo cultured human skin explant, and cultured melanocytes (MCs) and endothelial cells. METHODS: Melanin content and cluster of differentiation 31 (CD31)-positive cell numbers were measured in tail skins from UVB-irradiated mice treated by intragastral or topical TXA using immunofluorescent and Fontana-Masson staining. The conditioned medium (CM) was harvested from human umbilical vein endothelial cells treated with or without 3 mM TXA and was used to treat MCs for 48 hours. mRNA and protein levels of tyrosinase and microphthalmia-associated transcription factor were measured using quantitative real-time reverse transcription polymerase chain reaction and western blotting assays. HMB45- and CD31-positive cell numbers as well as melanin content were also examined in ex vivo cultured human skin explants. RESULTS: The hyperpigmented phenotype were significantly mitigated in UVB-irradiated tail skin plus intragastral TXA-treated mice compared with mice treated with UVB only or with UVB plus topical TXA. CD31-positive cell numbers correlated with the anti-melanogenic activity of TXA therapy. The data from cultured cells and skin tissues showed that suppression of endothelin-1 (ET-1) in vascular endothelial cells by TXA reduced melanogenesis and MC proliferation. CONCLUSION: Oral TXA outperforms topical TXA treatment in skin lightening, which contributes to suppression of ET-1 in dermal microvascular endothelial cells by TXA.

Avaliação da rotulagem de cosméticos clareadores de pele comercializados em Juazeiro, Bahia, Brasil / Evaluation of the labeling of skin lightening cosmetics marketed in Juazeiro, Bahia, Brazil

A hiperpigmentação da pele, principalmente na região facial, resulta em um incômodo estético que afeta a qualidade de vida do indivíduo, levando a busca por produtos clareadores. Este estudo avaliou a conformidade dos rótulos de cosméticos comercializados como "produtos clareadores de pele", bem como a existência de substâncias clareadoras proibidas neste tipo de produto. Foi realizada uma análise transversal descritiva qualitativa no período de abril a maio de 2022, em busca por cosméticos comercializados em estabelecimentos farmacêuticos e lojas de produtos cosméticos localizadas no município de Juazeiro/BA. Foram selecionados 18 produtos e os desvios de rotulagem identificados com base na legislação utilizada vigente à época do estudo, foram: ausência de informações sobre advertências/restrições de uso e número de registro incompleto, equivalente a 16,7% (n = 3) das amostras. A hidroquinona, proibida nesse tipo de produto, foi encontrada em um cosmético (5,5%). Embora a maioria das amostras analisadas esteja em conformidade com as exigências legais, os resultados evidenciam descumprimentos, indicando a necessidade de uma fiscalização mais rigorosa a fim de evitar possíveis danos à saúde do usuário.

Skin hyperpigmentation, particularly in the facial region, can be an aesthetic nuisance that affects an individual's quality of life, leading them to seek out whitening products. This study evaluated the compliance of cosmetics labels marketed as "skin lightening products", and assessed the presence of whitening substances prohibited in this type of product. A qualitative, descriptive, cross-sectional analysis was conducted between April and May 2022 in Juazeiro, Bahia, Brazil, focusing on cosmetics sold in pharmaceutical establishments and cosmetic product stores. Eighteen products were selected, and labeling deviations identified based on the legislation in force at the time of the study. These included a lack of information on warnings/use restrictions and incomplete registration numbers, affecting 16.7% (n = 3) of the samples. Hydroquinone, prohibited in this type of product by the legislation, was detected in one cosmetic (5.5%). Although most of the analyzed samples comply with legal requirements, the observed non-compliance highlights the need for more stringent inspection to prevent potential harm to user's health.

Comparative Study on Depigmenting Agents in Skin of Color.

Objective: Skin lightening agents are popular in southern Asia, but there is dearth of evidence on their effectiveness on Fitzpatrick IV/V skin types. This study was designed to assess the depigmenting efficacy of commercially available and specifically formulated ointments using the Mexameter® (MX 18). Methods: This single center prospective study was performed to test five commercially available preparations (Eldopaque®, Aziderm®, Garnier Dark Spot Corrector®, Ban a Tan Cream® and Neostrata Pigment Lightening Gel) on 28 healthy female volunteers in Phase 1, while five single active ingredients in lipophilic dispersion (hydroquinone 4%, ascorbyl palmitate 1%, resveratrol 1% arbutin 5% and azelaic acid 20%) were tested on a different group of 26 healthy female volunteers in Phase 2. The test agents were applied twice a day for five days per week and continued for six weeks in both study phases. Weekly Mexameter® measurements were obtained from test sites and negative controls. Results: Significant hypopigmentation when compared to untreated controls was observed with Aziderm cream (p<0.05, MWU) and the Neostrata Pigment Lightening Gel (p<0.05, MWU). All formulated preparations showed significant reduction in pigmentation; however, only the arbutin (5%) containing formulation revealed significant attenuation of pigmentation in comparison to the inactive control (p<0.05, MWU). Conclusion: All applications containing active ingredients showed significant skin lightening; however, only arbutin was able to demonstrate significant diminution of pigmentation when compared to the inactive control.

Updates and new medical treatments for vitiligo (Review).

Vitiligo is a multifactorial disease characterized by the loss of skin pigment, which results in achromic macules and patches. There are currently several medical treatments available, which aim to arrest progression and induce skin repigmentation. These treatments alone or combined have exhibited varying degrees of pigmentation, and the majority are safe and effective. All therapies for vitiligo are limited, and no known treatment can consistently produce repigmentation in all patients. Individualized treatment is appropriate according to the location, clinical presentation and the presence of disease activity. The present review summarizes the medical treatments available for vitiligo: Systemic and topic pharmacological therapies, physical and depigmentation treatments. Several treatments are still underway and have not yet been approved. However, due to the promising preliminary results, these are also mentioned in the present review.

Inhibition of melanogenesis by sodium 2-mercaptoethanesulfonate.

Sodium 2-mercaptoethanesulfonate (mesna) is a protective agent that is widely used in medicine because of its antioxidant effects. Recently, reactive oxygen species (ROS) were shown to increase pigmentation. Thus, ROS scavengers and inhibitors of ROS production may suppress melanogenesis. Forkhead box-O3a (FoxO3a) is an antimelanogenic factor that mediates ROS-induced skin pigmentation. In this study, we aimed to investigate the whitening effect of mesna and the signaling mechanism mediating this effect. Human melanoma (MNT-1) cells were used in this study. mRNA and protein expression were measured by real-time quantitative PCR and Western blotting analysis to track changes in FoxO3a-related signals induced by mesna. An immunofluorescence assay was performed to determine the nuclear translocation of FoxO3a. When MNT-1 melanoma cells were treated with mesna, melanin production and secretion decreased. These effects were accompanied by increases in FoxO3a activation and nuclear translocation, resulting in downregulation of four master genes of melanogenesis: MITF, TYR, TRP1, and TRP2. We found that mesna, an antioxidant and radical scavenger, suppresses melanin production and may therefore be a useful agent for the clinical treatment of hyperpigmentation disorders.

Skin lightening products' violations in Europe: An analysis of the rapid alert system for dangerous non-food products 2005-2018.

BACKGROUND: Skin lightening products containing dangerous levels of chemicals pose a serious health concern for consumers. However, to date, the extent of these products in Europe has not been extensively studied. The aim of this study was to determine whether harmful skin lightening products are available for sale in Europe and what violations exist regarding their composition. MATERIALS AND METHODS: We queried the Rapex database, which is the Rapid Alert System for dangerous non-food products among 31 European countries, to identify skin lightening cosmetics reported between 2005 and 2018, and presented a detailed summary of these notifications. RESULTS: In the years 2005-2018, of all violations regarding cosmetics, 26.3% concerned skin lightening products. In the database, 266 reports on skin lightening products were identified. Most of the notifications came from Germany (17.29%), France (17.29%), Portugal (15.41%), and the United Kingdom (11.65%). The majority of the registered products originated from non-European countries, mainly the Côte d'Ivoire (29.70%). The major reason for the violation was the content of hydroquinone, mercury, or clobetasol propionate. CONCLUSIONS: Hazardous skin lightening products that are not in line with European cosmetics legislation are available on the European market. Most of the products are imported. The main risk associated with these products is the content of hydroquinone, mercury, and clobetasol propionate. It is important to bear in mind that this study focuses on the Rapex system and other sources of information may exist. Based on our findings, a more comprehensive evaluation by international authorities is justified.

A systematic review of global legal regulations on the permissible level of heavy metals in cosmetics with particular emphasis on skin lightening products.

BACKGROUND: There is an urgent need to address the safety problems caused by the use of skin lightening cosmetics. Evidence suggests that some of them may contain heavy metals. OBJECTIVES: We conducted a systematic review of global legal regulations regarding the permissible level of mercury, lead, arsenic, and cadmium in cosmetic products, with particular emphasis on skin lightening preparations. METHODS: The systematic search of documents was a two-stage process. First, official websites of 17 regional organizations and subsequently regulations for countries with a population over 100 million were searched. RESULTS: Fifteen legislative acts, encompassing more than 67·2% of the global population were reviewed. Regulations were identified for 44/59 high income countries, 16/55 upper middle income countries, 9/45 lower income countries, 0/34 low income countries. The median adult literacy rate was 91·4% and 64·2% in countries with and without regulations, respectively. The use of mercury, lead, arsenic, and cadmium has been banned in 67, 67, 65, and 65 out of 69 countries, respectively. CONCLUSIONS: While regulations exist in most of the high income countries, in low income countries there is a lack of similar standards. In most countries for which these legal regulations have been identified, restrictions on the permissible level of heavy metals are strict. There is a need for enforcement of existing rules, and rigorous assessment of the effectiveness of these regulations.

[High school student and skin bleaching in Cameroon]. / Perceptions de la dépigmentation volontaire de la peau chez les lycéennes au Cameroun.

Introduction: Skin bleaching is a common practice in Africa, particularly in Cameroon. Studies show that it represents a danger for health, in terms of a demonstrated increased risk of dermatological diseases. However, increasing numbers of people are using skin bleaching in African cities, despite the fact that they are sometimes aware of the risk. This study proposed to transform the knowledge and perceptions of skin bleaching practices into educational strategies that can be used both by health professionals and educators. These strategies can also be used as preventive measures against skin bleaching among young schoolgirls. Methods: Data collection was based on a qualitative approach, in the form of a focus group discussion attended by 40 girls aged between 14 and 20 years, selected by convenient random sampling. Results: The results indicated that girls have an approximate knowledge about the consequences of skin bleaching on their health. On the contrary, they have a good knowledge about prevention, which can be used to develop a prevention strategy in order to reduce or eradicate skin bleaching, by educational awareness campaigns Conclusion: These elements can be used as a basis for better prevention and health promotion in schools; so that students adopt healthy behaviours and to prevent those students at risk.

Follow-up of solar lentigo depigmentation with a retinaldehyde-based cream by clinical evaluation and calibrated colour imaging.

BACKGROUND AND OBJECTIVE: To assess an objective method evaluating the effects of a retinaldehyde-based cream (RA-cream) on solar lentigines; 29 women randomly applied RA-cream on lentigines of one hand and a control cream on the other, once daily for 3 months. METHODS: A specific method enabling a reliable visualisation of the lesions was proposed, using high-magnification colour-calibrated camera imaging. Assessment was performed using clinical evaluation by Physician Global Assessment score and image analysis. Luminance determination on the numeric images was performed either on the basis of 5 independent expert's consensus borders or probability map analysis via an algorithm automatically detecting the pigmented area. RESULTS: Both image analysis methods showed a similar lightening of ΔL* = 2 after a 3-month treatment by RA-cream, in agreement with single-blind clinical evaluation. CONCLUSION: High-magnification colour-calibrated camera imaging combined with probability map analysis is a fast and precise method to follow lentigo depigmentation.