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Kazumasa Wakamatsu - One of the best experts on this subject based on the ideXlab platform.
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Biochemical Mechanism of Rhododendrol-Induced Leukoderma
MDPI AG, 2018Co-Authors: Shosuke Ito, Kazumasa WakamatsuAbstract:RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol (RD))—a skin-whitening ingredient—was reported to induce Leukoderma in some consumers. We have examined the biochemical basis of the RD-induced Leukoderma by elucidating the metabolic fate of RD in the course of tyrosinase-catalyzed oxidation. We found that the oxidation of racemic RD by mushroom tyrosinase rapidly produces RD-quinone, which gives rise to secondary quinone products. Subsequently, we confirmed that human tyrosinase is able to oxidize both enantiomers of RD. We then showed that B16 cells exposed to RD produce high levels of RD-pheomelanin and protein-SH adducts of RD-quinone. Our recent studies showed that RD-eumelanin—an oxidation product of RD—exhibits a potent pro-oxidant activity that is enhanced by ultraviolet-A radiation. In this review, we summarize our biochemical findings on the tyrosinase-dependent metabolism of RD and related studies by other research groups. The results suggest two major mechanisms of cytotoxicity to melanocytes. One is the cytotoxicity of RD-quinone through binding with sulfhydryl proteins that leads to the inactivation of sulfhydryl enzymes and protein denaturation that leads to endoplasmic reticulum stress. The other mechanism is the pro-oxidant activity of RD-derived melanins that leads to oxidative stress resulting from the depletion of antioxidants and the generation of reactive oxygen radicals
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Tyrosinase-Catalyzed Oxidation of the Leukoderma-Inducing Agent Raspberry Ketone Produces (E)-4-(3-Oxo-1-butenyl)-1,2-benzoquinone: Implications for Melanocyte Toxicity.
Chemical Research in Toxicology, 2017Co-Authors: Shosuke Ito, Maki Hinoshita, Erina Suzuki, Makoto Ojika, Kazumasa WakamatsuAbstract:The exposure of human skin to 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) is known to cause chemical/occupational Leukoderma. RK has a structure closely related to 4-(4-hydroxyphenyl)-2-butanol (rhododendrol), a skin whitening agent that was found to cause Leukoderma in the skin of consumers in 2013. Rhododendrol is a good substrate for tyrosinase and causes a tyrosinase-dependent cytotoxicity to melanocytes, cells that are responsible for skin pigmentation. Therefore, it is expected that RK exerts its cytotoxicity to melanocytes through the tyrosinase-catalyzed oxidation to cytotoxic o-quinones. The results of this study demonstrate that the oxidation of RK by mushroom tyrosinase rapidly produces 4-(3-oxobutyl)-1,2-benzoquinone (RK-quinone), which is converted within 10–20 min to (E)-4-(3-oxo-1-butenyl)-1,2-benzoquinone (DBL-quinone). These quinones were identified as their corresponding catechols after reduction by ascorbic acid. RK-quinone and DBL-quinone quantitatively bind to the small thio...
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Tyrosinase-Catalyzed Oxidation of the Leukoderma-Inducing Agent Raspberry Ketone Produces (E)‑4-(3-Oxo-1-butenyl)-1,2-benzoquinone: Implications for Melanocyte Toxicity
2017Co-Authors: Shosuke Ito, Maki Hinoshita, Erina Suzuki, Makoto Ojika, Kazumasa WakamatsuAbstract:The exposure of human skin to 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) is known to cause chemical/occupational Leukoderma. RK has a structure closely related to 4-(4-hydroxyphenyl)-2-butanol (rhododendrol), a skin whitening agent that was found to cause Leukoderma in the skin of consumers in 2013. Rhododendrol is a good substrate for tyrosinase and causes a tyrosinase-dependent cytotoxicity to melanocytes, cells that are responsible for skin pigmentation. Therefore, it is expected that RK exerts its cytotoxicity to melanocytes through the tyrosinase-catalyzed oxidation to cytotoxic o-quinones. The results of this study demonstrate that the oxidation of RK by mushroom tyrosinase rapidly produces 4-(3-oxobutyl)-1,2-benzoquinone (RK-quinone), which is converted within 10–20 min to (E)-4-(3-oxo-1-butenyl)-1,2-benzoquinone (DBL-quinone). These quinones were identified as their corresponding catechols after reduction by ascorbic acid. RK-quinone and DBL-quinone quantitatively bind to the small thiol N-acetyl-l-cysteine to form thiol adducts and can also bind to the thiol protein bovine serum albumin through its cysteinyl residue. DBL-quinone is more reactive than RK-quinone, as judged by their half-lives (6.2 min vs 10.5 min, respectively), and decays rapidly to form an oligomeric pigment (RK-oligomer). The RK-oligomer can oxidize GSH to GSSG with a concomitant production of hydrogen peroxide, indicating its pro-oxidant activity, similar to that of the RD-oligomer. These results suggest that RK is cytotoxic to melanocytes through the binding of RK-derived quinones to thiol proteins and the pro-oxidant activity of the RK-oligomer
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rhododenol induced Leukoderma in a mouse model mimicking japanese skin
Journal of Dermatological Science, 2016Co-Authors: Yuko Abe, Shosuke Ito, Kazumasa Wakamatsu, Ken Okamura, Yutaka Hozumi, Masakazu Kawaguchi, Hitomi Aoki, Takahiro Kunisada, Kayoko Matsunaga, Tamio SuzukiAbstract:Abstract Background Rhododendrol, 4-(4-hydroxyphenyl)-2-butanol, Rhododenol® (RD), a naturally occurring phenolic compound, was developed as a tyrosinase inhibitor for skin-lightening/whitening cosmetics. In 2013, skin depigmentation was reported in consumers using RD-containing skin-brightening cosmetics; this condition is called RD-induced Leukoderma. Objective The etiology of RD-induced Leukoderma is still largely unknown. Here, to assess the depigmentation potential of RD, we developed a new mouse model of Leukoderma by topically applying RD. Methods Hairless hk14-SCF Tg mice with melanocytes distributed in the epidermis were used for this study. RD was applied on the dorsal skin of the mice daily for 28 days. Then, immunohistological, biochemical, and electron microscopic analyses were performed on biopsy samples taken from these mice. Results The depigmentation in the RD-treated sites appeared on Day 14. Histological examination indicated a loss of epidermal melanocytes at Day 7. On the other hand, the melanocyte number did not decrease in the albino mice having the same background as the hairless hk14-SCF Tg, but without tyrosinase activity. Biochemical analyses showed that the eumelanin content decreased in the RD-treated sites and metabolites of RD-quinone, i.e., non-protein thiol adducts and protein-SH adducts, were produced. Electron microscopic analyses revealed double-membrane-walled structures containing electron-dense material, which might be typical for melanin-containing autophagosomes and a dilated endoplasmic reticulum (ER), which would indicate ER stress. Conclusions These data suggested that RD exerted tyrosinase-dependent melanocyte cytotoxicity and that tyrosinase-dependent accumulation of ER stress from activation of the autophagy pathway contributed to melanocyte cytotoxicity.
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A convenient screening method to differentiate phenolic skin whitening tyrosinase inhibitors from Leukoderma-inducing phenols
Journal of Dermatological Science, 2015Co-Authors: Shosuke Ito, Kazumasa WakamatsuAbstract:Abstract Background Tyrosinase is able to oxidize a great number of phenols and catechols to form ortho -quinones. Ortho -quinones are highly reactive compounds that exert cytotoxicity through binding with thiol enzymes and the production of reactive oxygen species. Certain phenolic (and catecholic) compounds are known to induce contact/occupational Leukoderma through activation to ortho -quinones. Objective We report a convenient screening method to follow the oxidation of those Leukoderma-inducing phenols by mushroom tyrosinase. Methods Oxidation of phenolic compounds by mushroom tyrosinase was followed periodically by UV–vis spectrophotometry. The production of ortho -quinones were confirmed by their absorptions around 400–420nm. HPLC analysis after reduction with NaBH 4 detected the corresponding catechols. Results Leukoderma-inducing phenols, rhododendrol, raspberry ketone, 4-methoxyphenol, 4-benzyloxyphenol, 4- tert -butylphenol, and 4- tert -butylcatechol, were readily oxidized by mushroom tyrosinase to form ortho -quinones. On the other hand, phenolic skin whitening tyrosinase inhibitors, ellagic acid, 4- n -butylresorcinol, potassium 4-methoxysalicylate, and 2,2′-dihydroxy-5,5′-di- n -propylbiphenyl, were not oxidized by mushroom tyrosinase, while arbutin was only slowly oxidized. Conclusion This study has provided a convenient screening method to differentiate phenolic skin whitening tyrosinase inhibitors from Leukoderma-inducing phenols. A common chemical feature of the latter group of compounds is that they are readily oxidized by tyrosinase to form reactive ortho -quinone species. The present results point out the necessity that tyrosinase inhibitors should also be examined as substrates if they are phenolic compounds.
Shosuke Ito - One of the best experts on this subject based on the ideXlab platform.
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rhododendrol induced Leukoderma update ii pathophysiology mechanisms risk evaluation and possible mechanism based treatments in comparison with vitiligo
Journal of Dermatology, 2021Co-Authors: Shintaro Inoue, Shosuke Ito, Atsushi Tanemura, Ichiro Katayama, Yuko Abe, Tamio Suzuki, Yasuyuki Sumikawa, Momoko Yoshikawa, Kayoko Suzuki, Akiko YagamiAbstract:A small proportion of individuals utilizing cosmetics containing rhododendrol developed Leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced Leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced Leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.
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Biochemical Mechanism of Rhododendrol-Induced Leukoderma
MDPI AG, 2018Co-Authors: Shosuke Ito, Kazumasa WakamatsuAbstract:RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol (RD))—a skin-whitening ingredient—was reported to induce Leukoderma in some consumers. We have examined the biochemical basis of the RD-induced Leukoderma by elucidating the metabolic fate of RD in the course of tyrosinase-catalyzed oxidation. We found that the oxidation of racemic RD by mushroom tyrosinase rapidly produces RD-quinone, which gives rise to secondary quinone products. Subsequently, we confirmed that human tyrosinase is able to oxidize both enantiomers of RD. We then showed that B16 cells exposed to RD produce high levels of RD-pheomelanin and protein-SH adducts of RD-quinone. Our recent studies showed that RD-eumelanin—an oxidation product of RD—exhibits a potent pro-oxidant activity that is enhanced by ultraviolet-A radiation. In this review, we summarize our biochemical findings on the tyrosinase-dependent metabolism of RD and related studies by other research groups. The results suggest two major mechanisms of cytotoxicity to melanocytes. One is the cytotoxicity of RD-quinone through binding with sulfhydryl proteins that leads to the inactivation of sulfhydryl enzymes and protein denaturation that leads to endoplasmic reticulum stress. The other mechanism is the pro-oxidant activity of RD-derived melanins that leads to oxidative stress resulting from the depletion of antioxidants and the generation of reactive oxygen radicals
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Tyrosinase-Catalyzed Oxidation of the Leukoderma-Inducing Agent Raspberry Ketone Produces (E)-4-(3-Oxo-1-butenyl)-1,2-benzoquinone: Implications for Melanocyte Toxicity.
Chemical Research in Toxicology, 2017Co-Authors: Shosuke Ito, Maki Hinoshita, Erina Suzuki, Makoto Ojika, Kazumasa WakamatsuAbstract:The exposure of human skin to 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) is known to cause chemical/occupational Leukoderma. RK has a structure closely related to 4-(4-hydroxyphenyl)-2-butanol (rhododendrol), a skin whitening agent that was found to cause Leukoderma in the skin of consumers in 2013. Rhododendrol is a good substrate for tyrosinase and causes a tyrosinase-dependent cytotoxicity to melanocytes, cells that are responsible for skin pigmentation. Therefore, it is expected that RK exerts its cytotoxicity to melanocytes through the tyrosinase-catalyzed oxidation to cytotoxic o-quinones. The results of this study demonstrate that the oxidation of RK by mushroom tyrosinase rapidly produces 4-(3-oxobutyl)-1,2-benzoquinone (RK-quinone), which is converted within 10–20 min to (E)-4-(3-oxo-1-butenyl)-1,2-benzoquinone (DBL-quinone). These quinones were identified as their corresponding catechols after reduction by ascorbic acid. RK-quinone and DBL-quinone quantitatively bind to the small thio...
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Tyrosinase-Catalyzed Oxidation of the Leukoderma-Inducing Agent Raspberry Ketone Produces (E)‑4-(3-Oxo-1-butenyl)-1,2-benzoquinone: Implications for Melanocyte Toxicity
2017Co-Authors: Shosuke Ito, Maki Hinoshita, Erina Suzuki, Makoto Ojika, Kazumasa WakamatsuAbstract:The exposure of human skin to 4-(4-hydroxyphenyl)-2-butanone (raspberry ketone, RK) is known to cause chemical/occupational Leukoderma. RK has a structure closely related to 4-(4-hydroxyphenyl)-2-butanol (rhododendrol), a skin whitening agent that was found to cause Leukoderma in the skin of consumers in 2013. Rhododendrol is a good substrate for tyrosinase and causes a tyrosinase-dependent cytotoxicity to melanocytes, cells that are responsible for skin pigmentation. Therefore, it is expected that RK exerts its cytotoxicity to melanocytes through the tyrosinase-catalyzed oxidation to cytotoxic o-quinones. The results of this study demonstrate that the oxidation of RK by mushroom tyrosinase rapidly produces 4-(3-oxobutyl)-1,2-benzoquinone (RK-quinone), which is converted within 10–20 min to (E)-4-(3-oxo-1-butenyl)-1,2-benzoquinone (DBL-quinone). These quinones were identified as their corresponding catechols after reduction by ascorbic acid. RK-quinone and DBL-quinone quantitatively bind to the small thiol N-acetyl-l-cysteine to form thiol adducts and can also bind to the thiol protein bovine serum albumin through its cysteinyl residue. DBL-quinone is more reactive than RK-quinone, as judged by their half-lives (6.2 min vs 10.5 min, respectively), and decays rapidly to form an oligomeric pigment (RK-oligomer). The RK-oligomer can oxidize GSH to GSSG with a concomitant production of hydrogen peroxide, indicating its pro-oxidant activity, similar to that of the RD-oligomer. These results suggest that RK is cytotoxic to melanocytes through the binding of RK-derived quinones to thiol proteins and the pro-oxidant activity of the RK-oligomer
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rhododenol induced Leukoderma in a mouse model mimicking japanese skin
Journal of Dermatological Science, 2016Co-Authors: Yuko Abe, Shosuke Ito, Kazumasa Wakamatsu, Ken Okamura, Yutaka Hozumi, Masakazu Kawaguchi, Hitomi Aoki, Takahiro Kunisada, Kayoko Matsunaga, Tamio SuzukiAbstract:Abstract Background Rhododendrol, 4-(4-hydroxyphenyl)-2-butanol, Rhododenol® (RD), a naturally occurring phenolic compound, was developed as a tyrosinase inhibitor for skin-lightening/whitening cosmetics. In 2013, skin depigmentation was reported in consumers using RD-containing skin-brightening cosmetics; this condition is called RD-induced Leukoderma. Objective The etiology of RD-induced Leukoderma is still largely unknown. Here, to assess the depigmentation potential of RD, we developed a new mouse model of Leukoderma by topically applying RD. Methods Hairless hk14-SCF Tg mice with melanocytes distributed in the epidermis were used for this study. RD was applied on the dorsal skin of the mice daily for 28 days. Then, immunohistological, biochemical, and electron microscopic analyses were performed on biopsy samples taken from these mice. Results The depigmentation in the RD-treated sites appeared on Day 14. Histological examination indicated a loss of epidermal melanocytes at Day 7. On the other hand, the melanocyte number did not decrease in the albino mice having the same background as the hairless hk14-SCF Tg, but without tyrosinase activity. Biochemical analyses showed that the eumelanin content decreased in the RD-treated sites and metabolites of RD-quinone, i.e., non-protein thiol adducts and protein-SH adducts, were produced. Electron microscopic analyses revealed double-membrane-walled structures containing electron-dense material, which might be typical for melanin-containing autophagosomes and a dilated endoplasmic reticulum (ER), which would indicate ER stress. Conclusions These data suggested that RD exerted tyrosinase-dependent melanocyte cytotoxicity and that tyrosinase-dependent accumulation of ER stress from activation of the autophagy pathway contributed to melanocyte cytotoxicity.
Tamio Suzuki - One of the best experts on this subject based on the ideXlab platform.
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rhododendrol induced Leukoderma update ii pathophysiology mechanisms risk evaluation and possible mechanism based treatments in comparison with vitiligo
Journal of Dermatology, 2021Co-Authors: Shintaro Inoue, Shosuke Ito, Atsushi Tanemura, Ichiro Katayama, Yuko Abe, Tamio Suzuki, Yasuyuki Sumikawa, Momoko Yoshikawa, Kayoko Suzuki, Akiko YagamiAbstract:A small proportion of individuals utilizing cosmetics containing rhododendrol developed Leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced Leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced Leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.
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rhododendrol induced Leukoderma update i clinical findings and treatment
Journal of Dermatology, 2021Co-Authors: Kayoko Matsunaga, Atsushi Tanemura, Yuko Abe, Tamio Suzuki, Yasuyuki Sumikawa, Momoko Yoshikawa, Kayoko Suzuki, Akiko Yagami, Akiko Ito, Yukiko MasuiAbstract:Individuals who used skin-whitening cosmetics (quasi-drugs) containing 2% rhododendrol-containing agents, developed Leukoderma at a higher frequency than those who have used other skin-whitening cosmetics. The Rhododenol Research Team (RD-Team) was formed and commissioned by Kanebo Cosmetics Inc. to conduct research in treatments of rhododendrol-induced Leukoderma (RDL), to evaluate effective treatment options from a medical standpoint, and provide information to a wide range of people. In this study, we evaluated the efficacy of various treatments for RDL from a medical perspective, based on the information published in the literature as original or review articles. We searched the PubMed (international) and the Igaku Chuo Zasshi (ICHUSHI) (Japanese) databases using the keywords "Rhododenol" and "rhododendrol", for articles published between July 2013 and November 2020. We discuss the main clinical findings and treatments (topical, oral, phototherapy, and surgical) of this condition based on the literature review. We found that ultraviolet light therapy is the most effective treatment for RDL. We have also summarized reports of the efficacy of oral vitamin D3 in RDL. A topical prostaglandin derivative has been reported in a new study to be effective. We have provided guidance for patients using self-tanning and skin-whitening agents to improve their quality of life. Finally, we have highlighted the importance of providing patients with information on contact dermatitis and instructing them to discontinue product use immediately if they develop any symptoms of contact dermatitis while using skin-whitening agents.
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Leukoderma induced by rhododendrol is different from Leukoderma of vitiligo in pathogenesis a novel comparative morphological study
Journal of Cutaneous Pathology, 2019Co-Authors: Reiko Tsutsumi, Yuko Abe, Yutaka Hozumi, Tamio Suzuki, Kazunari Sugita, Nanako Yamada, Yuichi Yoshida, Osamu YamamotoAbstract:Background Rhododendrol (rhododenol), an inhibitor of tyrosinase activity, is used as a skin-whitening component. Many cases of Leukoderma after the application have been reported, termed rhododenol-induced Leukoderma (RIL). The aim of this study was to clarify the pathogenesis of RIL morphologically through comparison with vitiligo. Methods We examined 14 cases of RIL and 15 cases of vitiligo using routine histopathology and immunohistochemistry. Thirteen cases of RIL, six cases of vitiligo and specimens of the RIL mouse model were evaluated by electron microscopy. Results There were common findings in RIL and vitiligo at the light-microscopic level: (a) vacuolar changes in the dermo-epidermal junction, (b) melanophages in the papillary dermis, (c) perifollicular lymphocyte infiltration, (d) loss or decrease of basal melanin pigment and (e) decrease of melanocytes in the lesions. The ultrastructural observations showed specific findings of RIL: (a) remaining melanocytes in depigmented lesions, (b) inhomogeneous melanization in melanocytes and (c) degenerated melanosomes in melanocytes. Some of the findings were observed in a RIL mouse model. Furthermore, it is notable that cell organelles of melanocytes were intact in our RIL cases. Conclusion Morphological changes of RIL targeting melanosomes in melanocytes without degeneration of organelles reflect the reversible clinical course of most cases.
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rhododenol induced Leukoderma in a mouse model mimicking japanese skin
Journal of Dermatological Science, 2016Co-Authors: Yuko Abe, Shosuke Ito, Kazumasa Wakamatsu, Ken Okamura, Yutaka Hozumi, Masakazu Kawaguchi, Hitomi Aoki, Takahiro Kunisada, Kayoko Matsunaga, Tamio SuzukiAbstract:Abstract Background Rhododendrol, 4-(4-hydroxyphenyl)-2-butanol, Rhododenol® (RD), a naturally occurring phenolic compound, was developed as a tyrosinase inhibitor for skin-lightening/whitening cosmetics. In 2013, skin depigmentation was reported in consumers using RD-containing skin-brightening cosmetics; this condition is called RD-induced Leukoderma. Objective The etiology of RD-induced Leukoderma is still largely unknown. Here, to assess the depigmentation potential of RD, we developed a new mouse model of Leukoderma by topically applying RD. Methods Hairless hk14-SCF Tg mice with melanocytes distributed in the epidermis were used for this study. RD was applied on the dorsal skin of the mice daily for 28 days. Then, immunohistological, biochemical, and electron microscopic analyses were performed on biopsy samples taken from these mice. Results The depigmentation in the RD-treated sites appeared on Day 14. Histological examination indicated a loss of epidermal melanocytes at Day 7. On the other hand, the melanocyte number did not decrease in the albino mice having the same background as the hairless hk14-SCF Tg, but without tyrosinase activity. Biochemical analyses showed that the eumelanin content decreased in the RD-treated sites and metabolites of RD-quinone, i.e., non-protein thiol adducts and protein-SH adducts, were produced. Electron microscopic analyses revealed double-membrane-walled structures containing electron-dense material, which might be typical for melanin-containing autophagosomes and a dilated endoplasmic reticulum (ER), which would indicate ER stress. Conclusions These data suggested that RD exerted tyrosinase-dependent melanocyte cytotoxicity and that tyrosinase-dependent accumulation of ER stress from activation of the autophagy pathway contributed to melanocyte cytotoxicity.
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an immune pathological and ultrastructural skin analysis for rhododenol induced Leukoderma patients
Journal of Dermatological Science, 2015Co-Authors: Atsushi Tanemura, Fei Yang, Lingli Yang, Yuiko Nagata, Mari Watayakaneda, Kazuyoshi Fukai, Daisuke Tsuruta, Rintaro Ohe, Mitsunori Yamakawa, Tamio SuzukiAbstract:As reported in the mass media on July 2013, numerous consumers who had used the cosmetic ingredient containing rhododendrol (4-(4-hydroxyphenyl)-2-butanol, Trade name; rhododenol), which is a melanin inhibitor isolated from Acer nikoense Maxim, released from Kanebo Cosmetics Inc. (Tokyo, Japan) noticed Leukoderma patches on their face, neck and hands. We have experienced 32 cases that developed Leukoderma after using such cosmetics so far and skin biopsy samples in some cases were obtained from both Leukoderma and pigmented lesions. A histopathological analysis for skin lesions obtained from such patients notably showed basal hypo-pigmentation, melanin incontinence, and remaining melanocytes in most patients which is not relevant in vitiligo vulgaris. Subsequently, we comprehensively carried out immunohistochemical analyses of immune-competent cells infiltration to assess the effect of the cellular immune response to inducible hypopigmentation. Furthermore, detailed morphological observations performed by electron-microscopy notably showed the presence of melanocytes with only a small number of melanosomes, dermal fibroblasts containing melanosome globules and melanophages whereas no damage associated with melanosome transfer and the basal layer apparatus. These findings provide a cue to diagnose as rhododenol-induced Leukoderma differentiate from vitiligo vulgaris and for rhododendrol to induce local immunity in addition to melanocyte damage.
Yuko Abe - One of the best experts on this subject based on the ideXlab platform.
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rhododendrol induced Leukoderma update ii pathophysiology mechanisms risk evaluation and possible mechanism based treatments in comparison with vitiligo
Journal of Dermatology, 2021Co-Authors: Shintaro Inoue, Shosuke Ito, Atsushi Tanemura, Ichiro Katayama, Yuko Abe, Tamio Suzuki, Yasuyuki Sumikawa, Momoko Yoshikawa, Kayoko Suzuki, Akiko YagamiAbstract:A small proportion of individuals utilizing cosmetics containing rhododendrol developed Leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced Leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced Leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.
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rhododendrol induced Leukoderma update i clinical findings and treatment
Journal of Dermatology, 2021Co-Authors: Kayoko Matsunaga, Atsushi Tanemura, Yuko Abe, Tamio Suzuki, Yasuyuki Sumikawa, Momoko Yoshikawa, Kayoko Suzuki, Akiko Yagami, Akiko Ito, Yukiko MasuiAbstract:Individuals who used skin-whitening cosmetics (quasi-drugs) containing 2% rhododendrol-containing agents, developed Leukoderma at a higher frequency than those who have used other skin-whitening cosmetics. The Rhododenol Research Team (RD-Team) was formed and commissioned by Kanebo Cosmetics Inc. to conduct research in treatments of rhododendrol-induced Leukoderma (RDL), to evaluate effective treatment options from a medical standpoint, and provide information to a wide range of people. In this study, we evaluated the efficacy of various treatments for RDL from a medical perspective, based on the information published in the literature as original or review articles. We searched the PubMed (international) and the Igaku Chuo Zasshi (ICHUSHI) (Japanese) databases using the keywords "Rhododenol" and "rhododendrol", for articles published between July 2013 and November 2020. We discuss the main clinical findings and treatments (topical, oral, phototherapy, and surgical) of this condition based on the literature review. We found that ultraviolet light therapy is the most effective treatment for RDL. We have also summarized reports of the efficacy of oral vitamin D3 in RDL. A topical prostaglandin derivative has been reported in a new study to be effective. We have provided guidance for patients using self-tanning and skin-whitening agents to improve their quality of life. Finally, we have highlighted the importance of providing patients with information on contact dermatitis and instructing them to discontinue product use immediately if they develop any symptoms of contact dermatitis while using skin-whitening agents.
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immunohistochemical analysis of rhododendrol induced Leukoderma in improved and aggravated cases
Journal of Dermatological Science, 2020Co-Authors: Masahito Yasuda, Atsushi Tanemura, Akiko Sekiguchi, Chikako Kishi, Sayaka Toki, Noriko Arase, Aya Takahashi, Fei Yang, Masahiro Hayashi, Yuko AbeAbstract:Abstract Background Rhododendrol (RD) is cytotoxic to melanocytes and can cause Leukoderma at the application site. Patients with RD-induced Leukoderma usually recover after discontinuation of application (improved cases). However, occasionally lesions may expand or new lesions may develop in unapplied sites (aggravated cases). Objective To understand the pathomechanism of RD-induced Leukoderma in aggravatedcases. Methods We performed immunohistochemical study to compare the expression of the catalytic subunit of glutamate cysteine ligase (GCLC), E-cadherin, and mast cell tryptase in 22 improved cases, 16 aggravated cases, and 39 normal controls. Results GCLC expression in melanocytes surrounding Leukoderma was higher in improved cases than in normal controls and aggravated cases. E-cadherin expression in melanocytes was upregulated both in improved and aggravated cases and increased levels of degranulated mast cells were observed in aggravated cases. Conclusion Our results indicate that downregulation of GCLC expression due to low levels of glutathione along with reduced melanocyte migration and increased E-cadherin expression can aggravate RD-induced Leukoderma. Additionally, increased degranulation of mast cells may prolong the persistence of RD-induced Leukoderma.
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genome wide association study identifies cdh13 as a susceptibility gene for rhododendrol induced Leukoderma
Pigment Cell & Melanoma Research, 2020Co-Authors: Ken Okamura, Atsushi Tanemura, Yuko Abe, Kazuyoshi Fukai, Akiko Yagami, Kayoko Matsunaga, Izumi Naka, Jun Ohashi, Yui Kobayashi, Ichiro KatayamaAbstract:Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol; trade name: Rhododenol [RD]), which is used in topical skin-lightening cosmetics, was unexpectedly reported in Japan to induce Leukoderma or vitiligo called RD-induced Leukoderma (RIL) after repeated application. To our knowledge, no studies have investigated chemical-induced vitiligo pathogenesis on a genome-wide scale. Here, we conducted a genome-wide association study (GWAS) for 147 cases and 112 controls. CDH13, encoding a glycosylphosphatidylinositol-anchored protein called T-cadherin (T-cad), was identified as the strongest RIL susceptibility gene. RD sensitivity was remarkably increased by T-cad knockdown in cultured normal human melanocytes. Furthermore, we confirmed tyrosinase upregulation and downregulation of the anti-apoptotic molecules (BCL-2 and BCL-XL), suggesting that T-cad is associated with RD via tyrosinase or apoptotic pathway regulation. Finally, monobenzyl ether of hydroquinone sensitivity also tended to increase with T-cad knockdown, suggesting that the T-cad could be a candidate susceptibility gene for RIL and other chemical-induced vitiligo forms. This is the first GWAS for chemical-induced vitiligo, and it could be a useful model for studying the disease's genetic aspects.
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Leukoderma induced by rhododendrol is different from Leukoderma of vitiligo in pathogenesis a novel comparative morphological study
Journal of Cutaneous Pathology, 2019Co-Authors: Reiko Tsutsumi, Yuko Abe, Yutaka Hozumi, Tamio Suzuki, Kazunari Sugita, Nanako Yamada, Yuichi Yoshida, Osamu YamamotoAbstract:Background Rhododendrol (rhododenol), an inhibitor of tyrosinase activity, is used as a skin-whitening component. Many cases of Leukoderma after the application have been reported, termed rhododenol-induced Leukoderma (RIL). The aim of this study was to clarify the pathogenesis of RIL morphologically through comparison with vitiligo. Methods We examined 14 cases of RIL and 15 cases of vitiligo using routine histopathology and immunohistochemistry. Thirteen cases of RIL, six cases of vitiligo and specimens of the RIL mouse model were evaluated by electron microscopy. Results There were common findings in RIL and vitiligo at the light-microscopic level: (a) vacuolar changes in the dermo-epidermal junction, (b) melanophages in the papillary dermis, (c) perifollicular lymphocyte infiltration, (d) loss or decrease of basal melanin pigment and (e) decrease of melanocytes in the lesions. The ultrastructural observations showed specific findings of RIL: (a) remaining melanocytes in depigmented lesions, (b) inhomogeneous melanization in melanocytes and (c) degenerated melanosomes in melanocytes. Some of the findings were observed in a RIL mouse model. Furthermore, it is notable that cell organelles of melanocytes were intact in our RIL cases. Conclusion Morphological changes of RIL targeting melanosomes in melanocytes without degeneration of organelles reflect the reversible clinical course of most cases.
Atsushi Tanemura - One of the best experts on this subject based on the ideXlab platform.
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rhododendrol induced Leukoderma update ii pathophysiology mechanisms risk evaluation and possible mechanism based treatments in comparison with vitiligo
Journal of Dermatology, 2021Co-Authors: Shintaro Inoue, Shosuke Ito, Atsushi Tanemura, Ichiro Katayama, Yuko Abe, Tamio Suzuki, Yasuyuki Sumikawa, Momoko Yoshikawa, Kayoko Suzuki, Akiko YagamiAbstract:A small proportion of individuals utilizing cosmetics containing rhododendrol developed Leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced Leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced Leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.
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rhododendrol induced Leukoderma update i clinical findings and treatment
Journal of Dermatology, 2021Co-Authors: Kayoko Matsunaga, Atsushi Tanemura, Yuko Abe, Tamio Suzuki, Yasuyuki Sumikawa, Momoko Yoshikawa, Kayoko Suzuki, Akiko Yagami, Akiko Ito, Yukiko MasuiAbstract:Individuals who used skin-whitening cosmetics (quasi-drugs) containing 2% rhododendrol-containing agents, developed Leukoderma at a higher frequency than those who have used other skin-whitening cosmetics. The Rhododenol Research Team (RD-Team) was formed and commissioned by Kanebo Cosmetics Inc. to conduct research in treatments of rhododendrol-induced Leukoderma (RDL), to evaluate effective treatment options from a medical standpoint, and provide information to a wide range of people. In this study, we evaluated the efficacy of various treatments for RDL from a medical perspective, based on the information published in the literature as original or review articles. We searched the PubMed (international) and the Igaku Chuo Zasshi (ICHUSHI) (Japanese) databases using the keywords "Rhododenol" and "rhododendrol", for articles published between July 2013 and November 2020. We discuss the main clinical findings and treatments (topical, oral, phototherapy, and surgical) of this condition based on the literature review. We found that ultraviolet light therapy is the most effective treatment for RDL. We have also summarized reports of the efficacy of oral vitamin D3 in RDL. A topical prostaglandin derivative has been reported in a new study to be effective. We have provided guidance for patients using self-tanning and skin-whitening agents to improve their quality of life. Finally, we have highlighted the importance of providing patients with information on contact dermatitis and instructing them to discontinue product use immediately if they develop any symptoms of contact dermatitis while using skin-whitening agents.
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immunohistochemical analysis of rhododendrol induced Leukoderma in improved and aggravated cases
Journal of Dermatological Science, 2020Co-Authors: Masahito Yasuda, Atsushi Tanemura, Akiko Sekiguchi, Chikako Kishi, Sayaka Toki, Noriko Arase, Aya Takahashi, Fei Yang, Masahiro Hayashi, Yuko AbeAbstract:Abstract Background Rhododendrol (RD) is cytotoxic to melanocytes and can cause Leukoderma at the application site. Patients with RD-induced Leukoderma usually recover after discontinuation of application (improved cases). However, occasionally lesions may expand or new lesions may develop in unapplied sites (aggravated cases). Objective To understand the pathomechanism of RD-induced Leukoderma in aggravatedcases. Methods We performed immunohistochemical study to compare the expression of the catalytic subunit of glutamate cysteine ligase (GCLC), E-cadherin, and mast cell tryptase in 22 improved cases, 16 aggravated cases, and 39 normal controls. Results GCLC expression in melanocytes surrounding Leukoderma was higher in improved cases than in normal controls and aggravated cases. E-cadherin expression in melanocytes was upregulated both in improved and aggravated cases and increased levels of degranulated mast cells were observed in aggravated cases. Conclusion Our results indicate that downregulation of GCLC expression due to low levels of glutathione along with reduced melanocyte migration and increased E-cadherin expression can aggravate RD-induced Leukoderma. Additionally, increased degranulation of mast cells may prolong the persistence of RD-induced Leukoderma.
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genome wide association study identifies cdh13 as a susceptibility gene for rhododendrol induced Leukoderma
Pigment Cell & Melanoma Research, 2020Co-Authors: Ken Okamura, Atsushi Tanemura, Yuko Abe, Kazuyoshi Fukai, Akiko Yagami, Kayoko Matsunaga, Izumi Naka, Jun Ohashi, Yui Kobayashi, Ichiro KatayamaAbstract:Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol; trade name: Rhododenol [RD]), which is used in topical skin-lightening cosmetics, was unexpectedly reported in Japan to induce Leukoderma or vitiligo called RD-induced Leukoderma (RIL) after repeated application. To our knowledge, no studies have investigated chemical-induced vitiligo pathogenesis on a genome-wide scale. Here, we conducted a genome-wide association study (GWAS) for 147 cases and 112 controls. CDH13, encoding a glycosylphosphatidylinositol-anchored protein called T-cadherin (T-cad), was identified as the strongest RIL susceptibility gene. RD sensitivity was remarkably increased by T-cad knockdown in cultured normal human melanocytes. Furthermore, we confirmed tyrosinase upregulation and downregulation of the anti-apoptotic molecules (BCL-2 and BCL-XL), suggesting that T-cad is associated with RD via tyrosinase or apoptotic pathway regulation. Finally, monobenzyl ether of hydroquinone sensitivity also tended to increase with T-cad knockdown, suggesting that the T-cad could be a candidate susceptibility gene for RIL and other chemical-induced vitiligo forms. This is the first GWAS for chemical-induced vitiligo, and it could be a useful model for studying the disease's genetic aspects.
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An Extremely Rare Case of Leukoderma Induced by Cosmetics Containing Ascorbic Acid.
Case reports in dermatology, 2019Co-Authors: Madoka Takafuji, Atsushi Tanemura, Ichiro KatayamaAbstract:We report the case of a 73-year-old woman with Leukoderma induced by cosmetics containing ascorbic acid. She had noticed the sudden appearance of a hypopigmented macule on the cheek within 1 month after use of the cosmetics with the brand name Obaji C Serum. No history of use of rhododenol-containing cosmetics was declared. Histopathological analysis revealed that the number of matured melanocytes was apparently decreased, and T lymphocytes abundantly infiltrated mainly the perifollicular region. In addition to the discontinuation of using Obaji C Serum, phototherapy by excimer light was noticeably effective for repigmentation. To our knowledge, there has been no other report so far showing hypopigmented lesions induced by this cosmetic.