Monobenzone Research Articles

Role of kinin receptors in skin pigmentation

Previous studies have shown that all kinin system is constitutively expressed in the normal and inflamed skin, with a potential role in both physiological and pathological processes. However, the understanding regarding the involvement of the kinin system in skin pigmentation and pigmentation disorders remains incomplete. In this context, the present study was designed to determine the role of kinins in the Monobenzone (MBZ)-induced vitiligo-like model. Our findings showed that MBZ induces higher local skin depigmentation in kinin receptors knockout mice (KOB1R, KOB2R and KOB1B2R) than in wild type (WT). Remarkably, lower levels of melanin content and reduced ROS generation were detected in KOB1R and KOB2R mice treated with MBZ. In addition, both KOB1R and KOB2R show increased dermal cell infiltrate in vitiligo-like skin, when compared to WT-MBZ. Additionally, lack of B1R was associated with greater skin accumulation of IL-4, IL-6, and IL-17 by MBZ, while KOB1B2R presented lower levels of TNF and IL-1. Of note, the absence of both kinin B1 and B2 receptors demonstrates a protective effect by preventing the increase in polymorphonuclear and mononuclear cell infiltrations, as well as inflammatory cytokine levels induced by MBZ. In addition, in vitro assays confirm that B1R and B2R agonists increase intracellular melanin synthesis, while bradykinin significantly enhanced extracellular melanin levels and proliferation of B16F10 cells. Our findings highlight that the lack of kinin receptors caused more severe depigmentation in the skin, as well as genetic deletion of both B1/B2 receptors seems to be linked with changes in levels of constitutive melanin levels, suggesting the involvement of kinin system in crucial skin pigmentation pathways.

Efficacy and Safety of Diphenylcyclopropenone (DPCP) as a Depigmenting Therapy in Extensive Vitiligo

Abstract Background Patients with extensive vitiligo who have residual pigmentation affecting exposed areas especially acral sites or patients with vitiligo universalis often seek depigmentation. At present, there is no ideal depigmenting therapy available. Possible options include; monobenzyl ether of hydroquinone (MBEH) cream, phenol, cryotherapy and Q-switched lasers. Diphenylcyclopropenone (DPCP) has been reported to rarely cause vitiligo as a side effect during the treatment of alopecia areata. Aim The aim of the present work is to evaluate the efficacy and safety of DPCP as a depigmenting therapy in extensive Vitiligo. Patients and Methods This is a pilot single arm clinical trial study. Twenty patients with extensive vitiligo were recruited from the vitiligo outpatient clinic of Dermatology, Venereology and Andrology Department, Ain Shams University Hospitals. We used DPCP applied topically to residual pigmented patches (sensitization session then therapeutic sessions). Results Depigmentation occurred among 5 patients (25% of cases). Depigmentation occurred in different tested sites including the scalp, forearm and back. Itching and blister formation were the main side effects leading to intolerability to the DPCP treatment. Conclusion Cosmetic result of DPCP depigmentation was acceptable with no skin atrophy. Further studies could be done following other protocols using sensitization dose with less concentrations of DPCP to avoid patients' intolerance to the therapy.

Development and Validation of Stability indicating HPLC method for determination of related substances and assay of Monobenzone drug substance

Monobenzone, a mono benzyl ether of hydroquinone, is used as a topical drug for skin depigmentation. It increases the excretion of melanin from melanocytes. A novel stability-indicating high performance liquid chromatographic approach has been established in the current study to identify related compounds and assay of Monobenzone. The Agilent 1260 system was used for the HPLC analysis, and a gradient method using 0.1% orthophosphoric acid in water and acetonitrile as the eluent was used to separate Monobenzone from known contaminants and degradation products on a Zorbax SB-phenyl (250 mm x 4.6 mm) 5 μm column. The flow rate was set at 0.8 mL/min, the column oven temperature was 30 °C, and the detector wavelength was maintained at 215 nm. The relative retention times for Hydroquinone and Monobenzone dimer were around 0.35 and 1.86 respectively, while the Monobenzone retention time was approximately 10.4 min. The total run time was 30 min. For all known analytes spanning the concentration range from LOQ to 200% of the specification level, the calibration plot revealed a linear relationship (minimum r=0.999). All known analytes' LOD and LOQ were found to be within 0.06–0.10 μg/mL and 0.15–0.24 μg/mL, respectively. A recovery study determined the accuracy of the proposed method. For Hydroquinone and Monobenzone dimer, mean recovery was found to be in the range of 95.86%–99.89% and 93.02%–99.84% respectively. The repeatability study showed that the method is precise enough within acceptable limits. Studies on solution stability and robustness produced results that fell within acceptable bounds. The proposed method shows excellent linearity, accuracy, precision, specificity, robustness, LOD, LOQ and system suitability findings. Additionally, the forced degradation study showed that the approach was stability indicating in nature.

Identification of Monobenzone as a Novel Potential Anti-Acute Myeloid Leukaemia Agent That Inhibits RNR and Suppresses Tumour Growth in Mouse Xenograft Model.

Simple SummaryThe clinical treatment of acute myeloid leukaemia is still dominated by chemotherapy. Clinically used anti-leukaemia drugs have shortcomings such as myelosuppression, toxicity and drug resistance. Therefore, the need to develop other chemotherapeutic drugs to meet more clinical needs is urgent. Ribonucleotide reductase (RNR) consists of a catalytic large subunit M1 (RRM1) and a regulatory small subunit M2 (RRM2), which provides dNTPs for DNA synthesis. The rapid proliferation of cancer cells requires large amounts of dNTPs. Therefore, the use of RNR inhibitors is a promising strategy for the clinical treatment of various malignancies. Monobenzone is an FDA-approved depigmenting agent for vitiligo patients. In this study, we demonstrate that monobenzone is a potent inhibitor of RNR enzyme activity by targeting RRM2 protein, and thus has significant anti-leukaemia efficacy in vitro and in vivo. This finding suggests that monobenzone has the potential to be optimized as a novel anti-AML therapeutic drug in the future. Acute myeloid leukaemia (AML) is one of the most common types of haematopoietic malignancy. Ribonucleotide reductase (RNR) is a key enzyme required for DNA synthesis and cell proliferation, and its small subunit RRM2 plays a key role for the enzymatic activity. We predicted monobenzone (MB) as a potential RRM2 target compound based on the crystal structure of RRM2. In vitro, MB inhibited recombinant RNR activity (IC50 = 0.25 μM). Microscale thermophoresis indicated that MB inhibited RNR activity by binding to RRM2. MB inhibited cell proliferation (MTT IC50 = 6–18 μM) and caused dose-dependent DNA synthesis inhibition, cell cycle arrest, and apoptosis in AML cells. The cell cycle arrest was reversed by the addition of deoxyribonucleoside triphosphates precursors, suggesting that RNR was the intracellular target of the compound. Moreover, MB overcame drug resistance to the common AML drugs cytarabine and doxorubicin, and treatment with the combination of MB and the Bcl-2 inhibitor ABT-737 exerted a synergistic inhibitory effect. Finally, the nude mice xenografts study indicated that MB administration produced a significant inhibitory effect on AML growth with relatively weak toxicity. Thus, we propose that MB has the potential as a novel anti-AML therapeutic agent in the future.

Technologies of Visibility

Technologies of Visibility

Repigmentation by combined narrow‑band ultraviolet B/adipose‑derived stem cell transplantation in the mouse model: Role of Nrf2/HO‑1‑mediated Ca2+ homeostasis.

Vitiligo is a depigmentation disease commonly seen in clinical practice, mainly involving loss of functional epidermal pigment cells and hair follicle melanocytes. Narrow-band ultraviolet B (NB-UVB) has emerged as the first choice of treatment for vitiligo, but long-term exposure may have serious consequences. Recently, it was reported that adipose-derived stem cells (ADSCs) improve melanocyte growth and the efficacy of melanocyte transplantation. The present study aimed to examine the efficacy of NB-UVB/ADSC-transplantation combined therapy on a mouse vitiligo model and explore the underlying mechanisms by focusing on endoplasmic reticulum stress and cellular calcium (Ca2+) homeostasis. Vitiligo mice models were established by applying 40% monobenzone (MBZ) cream twice daily and treated with NB-UVB/ADSC combination therapy. Some treated mice were also given ML385, a nuclear factor erythroid 2 like 2 (Nr2) inhibitor. Histopathological changes were evaluated using a depigmentation evaluation score and observed with hematoxylin and eosin staining on skin tissues. ELISA was used to measure diagnostic markers in plasma. Flow cytometric assay was performed to quantify CD3+, CD4+ and CD8+ levels. Expression levels of associated proteins were detected with western blot and immunofluorescence. Treatment of mice with MBZ-induced depigmentation patches on the skin was accompanied with loss of redox balance and disruption of cellular Ca2+ homeostasis. Oxidative stress and Ca2+ unbalancing were improved after the mice were treated by NB-UVB/ADSCs transplantation combination therapy. ML385, strongly negated the protective effect of NB-UVB/ADSC transplantation combination therapy, indicating the critical role of Nr2 signaling. The findings improved the understanding of the pathogenesis of vitiligo and will guide future development of therapeutic strategies against it.

Effects of Monobenzyl ether of hydroquinone on 3T3 mouse fibroblast viability and ultrastructure

ABSTRACT Monobenzyl ether of hydroquinone (MBEH) is a topical depigmentation agent used by vitiligo patients to even the skin tone. We aimed to investigate the effects of MBEH on 3T3 mouse fibroblasts. Fibroblasts were treated with 250 µM, 500 µM, and 750 µM MBEH and vehicle (EtOH:DMSO) for 24 hours. Cell numbers of 250 µM, 500 µM, and 750 µM MBEH treated and vehicle groups decreased significantly compared to control group. TUNEL positive cell rate increased with MBEH concentration. In electron microscopic examination, control and vehicle groups showed active cells features, while mitochondrial swelling and cristae loss were seen in 250 µM MBEH-treated group. In cytoplasm of 500 µM MBEH-treated group, there were many multivesicular bodies and autophagic vacuoles. As an indication of apoptosis, cell membrane blebs and reduction in cell size were observed. In 750 μM MBEH-treated group, cells were completely degenerated. Our findings show that MBEH, which is used as a depigmentation agent to lighten the skin by destroying melanocytes, may also have dose-dependent negative effects on the viability of 3T3 mouse fibroblasts, and these may be mediated through autophagic and apoptotic cell death mechanisms.

Chemical induced pathognomonic features observed in human vitiligo are mediated through miR-2909 RNomics pathway

BackgroundChemicals like Monobenzyl Ether of Hydroquinone (MBEH) and 4-Tertiary Butyl Phenol (4-TBP) have been widely recognized to induce clinical lesions that resemble vitiligo, but exact molecular pathway through which these chemicals initiate vitiligo is still far from clear. ObjectivesSince vitiligo is widely considered as an autoimmune disease, this study was an attempt to understand miR-2909 RNomics in vitiligo pathogenesis using MBEH treated primary melanocytes as an archetype cellular model because MBEH causes pathological features indistinguishable from clinical vitiligo. MethodsPrimary melanocytes were treated with MBEH and 4-TBP and the role of miR-2909 RNomics at transcriptional and translational level was explored through qRT-PCR, western blot analysis, flow cytometry, immunocytochemistry, immunohistochemistry and in silico binding affinities. 4 mm punch biopsies were also obtained from lesional sites of vitiligo patients to validate the results observed in cell culture experiments. ResultsMBEH induced miR-2909 RNomics led to downregulation of MITF, TYR, TYRP1, and TYRP2 leading to decreased melanin synthesis which in turn is a characteristic trait of vitiligo. On the other hand, 4-TBP increased TGF-β which also has the intrinsic capacity to downregulate MITF leading to decreased melanin synthesis and thereby initiation of vitiligo. ConclusionBased upon our results we propose a molecular pathway which has the inherent capacity to resolve the mechanism through which these chemicals may induce vitiligo. This mechanism was also found to be involved in the lesional biopsies of vitiligo patients. These results could be exploited in better understanding the pathogenesis as well as in treatment of vitiligo.

Monobenzyl ether of hydroquinone 20 and 40% cream in depigmentation of patients with vitiligo: a randomized controlled trial

Background Depigmentation represents a final alternative for patients with widespread vitiligo, failing to attain satisfactory pigmentation and having a compromised quality of life. Monobenzyl ether of hydroquinone (MBEH) is the most widely used depigmenting agent, but little is known regarding specific features of its utilization.Objective To evaluate and compare two concentrations of MBEH cream (20 and 40%) regarding their effectiveness, tolerability, and effect on patients’ quality of life.Patients and methods In a double-blind randomized study, 40 patients indicated for depigmentation were equally divided into MBEH 20 and 40% groups. Patients’ responses were assessed bimonthly over 1 year or till complete depigmentation was attained through photography, point counting, and colorimetric assessment. Baseline and final evaluations by dermatology life quality index and visual analog scale were performed. Patients were followed up for 6 months. The study was registered under number ‘PACTR201808699550182.’Results A total of 39 patients completed the study. Significant color dilution, reduction of point counting and melanin indices, and improvement of dermatology life quality index and visual analog scale scores were obtained in both groups. The number of patients who achieved complete depigmentation and the degree of skin irritation was higher in MBEH 40% group, but no significant difference was found regarding the efficacy, adverse effects, or relapse between groups.Conclusion MBEH 20 and 40% concentrations proved to be effective in depigmentation; however, MBEH 20% is more suitable for face in terms of safety profile, whereas MBEH 40% can be employed for resistant cases as well as for hands and areas of thick skin.

Rapid repigmentation of vitiligo with tofacitinib plus low-dose narrowband ultraviolet B (nbUVB), even following depigmentation with monobenzyl ether of hydroquinone

Rapid repigmentation of vitiligo with tofacitinib plus low-dose narrowband ultraviolet B (nbUVB), even following depigmentation with monobenzyl ether of hydroquinone

Manejo despigmentante de vitiligo generalizado con monobenzil eter de hidroquinona

El vitiligo es una patología crónica, recidivante y difícil de tratar. El objetivo primario del tratamiento es inducir la repigmentación, sin embargo en casos extensos refractarios a tratamiento, se puede realizar despigmentación para corregir la discromía. Dentro de los tratamientos despigmentantes en vitiligo, a la fecha el único aprobado por la FDA es el Monobenzil éter de hidroquinona (monobenzona). Se expone el caso de una paciente con vitiligo extenso y refractario a tratamiento que fue manejado con monobenzona. El resultado fue exitoso durante tiempo prolongado, con recaída parcial al suspender el medicamento. La recaída remitió con el reinicio de la monobenzona. Sin nueva recaída actualmente con tratamiento de mantención 3v/semana. La monobenzona induce acromía secundaria a necrosis de los melanocitos. Se requiere su uso 1 a 2 veces al día por 6-12 meses para lograr la despigmentación. En pacientes adecuadamente seleccionados, es una alternativa válida para el manejo del vitiligo. Se presenta un caso exitoso de despigmentación con monobenzona. Actualmente, la paciente está muy satisfecha con los resultados.

Depigmentation Therapies for Vitiligo.

The general goals of medical management of vitiligo are to repigment vitiliginous areas of skin and to stabilize the progression of depigmentation. However, for some patients with vitiligo affecting extensive body surface areas who are unresponsive to repigmentation therapies, depigmentation of the remaining normal skin may be a better choice. Candidates for depigmentation therapy should be carefully screened and patient education is essential. Permanent topical therapies used for depigmentation include monobenzyl ether of hydroquinone, 4-methoxyphenol, and 88% phenol. Physical modalities, such as cryotherapy and lasers, are also being used successfully.

Patch Testing in Patients with Suspected Footwear Dermatitis: A Retrospective Study.

Background:Footwear dermatitis represents a common but often undiagnosed or misdiagnosed condition. Patch testing aids in its confirmation and identification of the offending allergen.Aims:This study aimed to find the frequency of positive patch test reactions in cases with suspected allergic contact dermatitis (ACD) to footwear, as well as the common responsible allergens.Materials and Methods:This is a retrospective record based study of 37 patients, with suspected ACD to footwear, who underwent patch testing with Indian standard series and Indian footwear series from July 2012 to July 2015.Results:The majority of patients (45.94%) belonged to the age group of 20–40 years. Dorsal aspects of feet (81.08%) and soles (18.92%) were the common sites involved. Patch test was positive in 18.92% patients. The most common causative allergens were hydroquinone monobenzylether (8.11%) and 4-aminoazobenzene (5.41%).Conclusion:Common chemicals implicated in ACD were rubber, rubber additives, and dyes. The principal culprit allergens were hydroquinone monobenzylether and 4-aminoazobenzene.

Different effects of five depigmentary compounds, rhododendrol, raspberry ketone, monobenzone, rucinol and AP736 on melanogenesis and viability of human epidermal melanocytes.

Numerous medications are used to treat hyperpigmentation. However, several reports have indicated that repeated application of some agents, such as rhododendrol (RD), raspberry ketone (RK) and monobenzone (MB), can be toxic to melanocytes. Although these agents had severe side effects in human trials, no current in vitro methods can predict the safety of such drugs. This study assessed the in vitro effects of five depigmentary compounds including leukoderma-inducing agents. In particular, we determined the effects of different concentrations and exposure times of different depigmentary agents on cell viability and melanogenesis in the presence and absence of ultraviolet B (UVB) radiation. Concentrations of RD, RK and MB that inhibit melanogenesis are similar to concentrations that are cytotoxic; however, concentrations of rucinol (RC) and AP736 that inhibit melanogenesis are much lower than concentrations that are cytotoxic. Furthermore, the concentrations that cause toxic effects depend on exposure duration, and prolonged exposure to RD, RK and MB had more cytotoxic effects than prolonged exposure to RC and AP736. The cytotoxic effects of RD and RK appear to be mediated by apoptosis due to increased expression of caspase-3 and caspase-8; UVB radiation increased the cytotoxicity of these agents and also increased caspase activity. Our results indicate that different leukoderma-inducing compounds have different effects on the viability of normal epidermal melanocytes and suggest that the in vitro assay used here can be used to predict whether an investigational compound that induces leukoderma may lead to adverse effects in human trials.

Comparison of topical application of tea polyphenol versus pimecrolimus versus tacrolimus for the treatment of monobenzone-induced vitiligo-like depigmentation in a mouse model

Objective To compare the therapeutic effect of topical application of tea polyphenol versus pimecrolimus versus tacrolimus for monobenzone-induced vitiligo-like depigmentation in mice. Methods Twenty-five 3-week-old female C57BL/6 mice were randomly and equally divided into 5 groups: negative control group, model group, tea polyphenol group, pimecrolimus group, tacrolimus group. Monobenzone 45% cream was applied to the back of mice in all the five groups except the negative control group once daily for 40 consecutive days to establish a model of vitiligo-like depigmentation. During the induction of depigmentation, the tea polyphenol group, pimecrolimus group and tacrolimus group were topically treated with tea polyphenol, pimecrolimus and tacrolimus respectively, and the model group remaining untreated. The depigmentation of hairs and skin was observed by naked eyes on a daily basis. Tissue specimens were obtained for histological examination from depigmented skin at non-application sites in mice after the end of the experiment. Hematoxylin-eosin staining was conducted to analyze lymphocytic infiltration, reflectance confocal microscopy to observe melanin and melanocytes in skin, and immunofluorescence assay to detect CD8+ T cell infiltration. Results Depigmentation occurred in both application sites and non-application sites of mice in the model group. Compared with the model group, the tacrolimus, pimecrolimus and tea polyphenol groups showed delayed depigmentation, reduced degree and area index of depigmentation, and attenuated lymphocytic infiltration and CD8+ T cell infiltration in depigmented maculae at application sites. In addition, the therapeutic effect of tacrolimus was stronger than that of pimecrolimus and tea polyphenol. Conclusion Tea polyphenol, pimecrolimus and tacrolimus are all effective for the treatment of vitiligo-like depigmentation in mice. Key words: Monobenzone; Tea polyphenol; Tacrolimus; Pimecrolimus; Vitiligo, animal model

Effect of epigallocatechin gallate and fructus psoraleae on the induction of vitiligo-like depigmentation by monobenzone in mice

Objective To study the effect of epigallocatechin gallate (EGCG) and fructus psoraleae on the induction of vitiligo-like depigmentation by monobenzone in mice.Methods Forty C57BL/6 mice were included in this study.Hairs in an area measuring 2 cm × 2 cm in size were shaved on the back of each of these mice.Then,the mice were randomly and equally divided into four groups to be topically treated with vaseline cream (negative control group),monobenzone 40％ cream (model group),EGCG 5％ cream followed by monobenzone 40％ cream (EGCG group),fructus psoraleae 7％ cream followed by monobenzone 40％ cream (fructus psoraleae group),on the shaved area,respectively,for 50 consecutive days.Depigmentation of skin and hairs was observed daily by naked eyes for 15 days after drug withdrawal.At the end of the study,all the mice were sacrificed,and skin specimens were resected from the tested regions in them.Hematoxylin and eosin (HE) staining was performed to observe lymphocyte infiltration,and immunofluorescence assay to estimate the frequency of CD8 + T cells.Results Depigmentation was observed in monobenzone-induced and-uninduced sites in the model group,and in monobenzone-induced sites in all the mice in the EGCG group and fructus psoraleae group,but in neither monobenzone-induced nor-uninduced sites ih the negative control group.The average time for the appearance of depigmentation at monobenzone-induced sites was 16.7,29.3 and 19.9 days in the model group,EGCG group and fructus psoraleae group respectively.The depigmentation area index at monobenzone-induced sites was 4.00 ± 0.00 in the model group,significantly different from that in the EGCG group and fructus psoraleae group (2.11 ± 0.54 and 2.84 ± 0.79,both P ＜ 0.05).Significant differences were also observed in depigmentation area index at monobenzone-induced sites among the model group,EGCG group and fructus psoraleae group (F =14.173,P ＜ 0.05),and at monobenzone-uninduced sites between fructus psoraleae group and EGCG group (P ＜ 0.05).The frequency (expressed as fluorescence intensity) of CD8+ T cells was significantly lower in the EGCG group and fructus psoraleae group than in the model group,and significantly different between EGCG group and fructus psoraleae group (P ＜ 0.05).Conclusions Both EGCG and fructus psoraleae,especially EGCG,can interfere with the induction of vitiligo-like depigmentation of skin and hairs by monobenzone in mice.The mouse model of vitiligolike depigmentaion in this study shows higher similarity to human vitiligo. Key words: Vitiligo; Propyl gallate; PSORALEA CORYLIFOLIA; Disease models, animal

Targeting melanocyte and melanoma stem cells by 8-hydroxy-2-dipropylaminotetralin

Monobenzyl ether of hydroquinone (MBEH) is cytotoxic towards melanocytes. Its treatment efficacy is limited by an inability to eradicate stem cells. By contrast, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-DPAT) affects melanocyte stem cell survival. MBEH and 8-DPAT were added to melanocytes and melanoma cells to compare cytotoxicity. Stem cell content among viable cells was determined by fluorocytometry using markers CD34, Pax3, and CD271. Immunostaining was used to identify stem cells in skin explants treated with MBEH or 8-DPAT ex vivo. Mice were exposed to MBEH or 8-DPAT and scanned for depigmentation before harvesting skin. MBEH exposure prompted a relative increase in stem cells among cultured melanocytes and melanoma cells, as treatment preferentially eliminated differentiated cells and spared the stem cells. Viability of this remaining, enriched stem cell population was however rapidly reduced by exposure to 8-DPAT within melanocyte and melanoma cell cultures. In human skin explants, the abundance of melanocyte stem cells was also visibly reduced after 8-DPAT treatment, in contrast to tissue exposed to MBEH. Meanwhile, significant depigmentation of the mouse pelage and loss of differentiated melanocytes was observed in vivo in response to topical application of MBEH, but not 8-DPAT. Prolonged application of the latter agent instead appeared to effectively reduce the abundance of melanocyte stem cells in the dermis. This furthers the idea that MBEH and 8-DPAT target complementary cell populations. Results indicate that combination treatment may demonstrate superior therapeutic activity by eliminating both differentiated and tumor initiating populations.

Enhanced bleaching treatment: opportunities for immune-assisted melanocyte suicide in vitiligo.

Depigmentation in vitiligo occurs by progressive loss of melanocytes from the basal layer of the skin, and can be psychologically devastating to patients. T cell-mediated autoimmunity explains the progressive nature of this disease. Rather than being confronted with periods of rapid depigmentation and bouts of repigmentation, patients with long-standing, treatment-resistant vitiligo can undergo depigmentation treatment. The objective is to remove residual pigmentation to achieve a cosmetically acceptable result--that of skin with a uniform appearance. In the United States, only the use of mono-benzyl ether of hydroquinone (MBEH) is approved for this purpose. However, satisfactory results can take time to appear, and there is a risk of repigmentation. MBEH induces necrotic melanocyte death followed by a cytotoxic T-cell response to remaining, distant melanocytes. As cytotoxic T-cell responses are instrumental to depigmentation, we propose that combining MBEH with immune adjuvant therapies will accelerate immune-mediated melanocyte destruction to achieve faster, more definitive depigmentation than with MBEH alone. As Toll-like Receptor (TLR) agonists--imiquimod, CpG, and Heat Shock Protein 70 (HSP 70)--all support powerful Th1 responses, we propose that using MBEH in combination with these agents can achieve superior depigmentation results for vitiligo patients.

Effect of local acupuncture on monobenzone-induced vitiligo-like depigmentation in mice

Objective To evaluate the effect of injuries on monobenzone-induced vitiligo-like depigmentation in mice.Methods Forty C57BL/6 mice were randomly and equally divided into four groups:negative control group topically treated with vaseline cream,model group induced by topical monobenzone (40％) cream,acupuncture group receiving acupuncture treatment (15 times) once every three days,and acupuncture combined with monobenzone group receiving both monobenzone induction and acupuncture treatment.The treatment lasted 50 days and mice were sacrificed 15 days after the end of treatment.Hair decolorization was observed with naked eyes,and skin decolorization with reflectance confocal microscopy (RCM) on a daily basis.Tissue specimens were obtained from depigmented skin at monobenzone-uninduced sites,and subjected to hematoxylin and eosin (HE) staining for the cvaluation of lymphocytic infiltration as well as immunofluorescence staining for the detection of CD8+ T cell expression.Statistical analysis was done by t test.Results Varying degrees of depigmentation were observed in both monobenzone-induced and-uninduced sites in both the model group and acupuncture combined with monobenzone group,and the latter group showed earlier,larger and more stable depigmentation than the former group.At 15 days after the end of treatment,the decolorization area index in the model group and acupuncture combined with monobenzone group was 3.45 ± 0.17 and 3.90 ± 0.25 at monobenzone-induced sites respectively(t =7.433,P ＜ 0.05),1.90-± 0.12 and 2.85 ± 0.27 at monobenzone-uninduced sites respectively (t =7.529,P ＜ 0.05).Significant differences were observed in the fluorescence intensity of CD8 + T cells at monobenzone-uninduced depigmented sites between the model group and acupuncture combined with monobenzone group (175.528 ± 10.711 vs.645.928 ± 12.652,t =8.105,P ＜ 0.05),and there was a more evident infiltrate with lymphocytes and CD8+T cells in the monobenzone-uninduced depigmented sites in the acupuncture combined with monobenzone group.Conclusion Local destruction of skin barrier may promote monobenzone-induced vitiligo-like decolorization in mice. Key words: Monobenzone; Acupuncture; Vitiligo; Models, animal

Effect of monobenzyl ether of hydroquinone for advanced vitiligo patients

Background: Vitiligo is a common depigmentation disorder occurring in about 1% of the population worldwide. The disease causes the appearance of white patches on the skin. If vitiligo involves most of the body, it might be easier to depigment the normal remaining skin rather than to attempt repigmentation. For depigmentation therapy, monobenzyl ether of hydroquinone (MBEH) remains the only drug that the Food and Drug Administration approved for depigmentation therapy within the United States. The mechanism of toxicity of MBEH has remained little understood.