Review
Dermatology
Shintaro Inoue, Ichiro Katayama, Tamio Suzuki, Atsushi Tanemura, Shosuke Ito, Yuko Abe, Yasuyuki Sumikawa, Momoko Yoshikawa, Kayoko Suzuki, Akiko Yagami, Yukiko Masui, Akiko Ito, Kayoko Matsunaga
Summary: This review examines the major considerations for developing rhododendrol-induced leukoderma, providing a wide range of information on pathophysiology, mechanisms, risk evaluation, and potential treatments. The review discusses cytotoxicity of rhododendrol, cytoprotective functions, involvement of the immune system, and potential novel treatments, addressing individual differences and the mechanisms underlying the condition. Understanding rhododendrol-induced leukoderma not only sheds light on the mechanisms of non-segmental vitiligo, but also suggests possible prevention and treatment strategies.
JOURNAL OF DERMATOLOGY
(2021)
Article
Dermatology
Tomoko Nishimaki-Mogami, Shosuke Ito, Hongyan Cui, Takumi Akiyama, Norimasa Tamehiro, Reiko Adachi, Kazumasa Wakamatsu, Yoshiaki Ikarashi, Kazunari Kondo
Summary: The study aimed to find an effective method to evaluate the formation of o-quinone by human tyrosinase and subsequent cellular reactions. Among the tested chemicals, seven leukoderma-inducing phenols were oxidized to o-quinone metabolites, leading to cellular glutathione reduction. Some of these phenols exhibited tyrosinase-dependent cytotoxicity.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Kei Nagatani, Yuko Abe, Takujiro Homma, Junichi Fujii, Tamio Suzuki
Summary: Oxidative metabolism of the skin-whitening ingredient rhododendrol (RD) by tyrosinase has led to leukoderma in a certain population of Japanese consumers. It is hypothesized that RD may act as a suicide substrate for tyrosinase, releasing a copper atom and hydrogen peroxide during its inactivation, resulting in melanocyte death. Experiments with human melanocytes confirmed the irreversible decrease in tyrosinase activity and cell death after incubation with RD. The copper chelator D-penicillamine suppressed RD-induced cell death without affecting tyrosinase activity, indicating the involvement of copper and hydrogen peroxide in melanocyte impairment. These findings suggest that copper chelation may provide relief for chemical leukoderma caused by other compounds.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Lihao Gu, Kazuhisa Maeda
Summary: It has been found that raspberry ketone is produced from rhododendrol in both mouse and human skin. The addition of nicotinamide adenine dinucleotide (NAD(+)), an oxidized form of a coenzyme of alcohol dehydrogenase, to human skin samples increased the conversion of rhododendrol to raspberry ketone. Chiral column analysis revealed a significant difference in the enantiomers of raspberry ketone in human skin, indicating that certain enantiomers are more susceptible to oxidation. These findings suggest that alcohol dehydrogenase in the skin plays a key role in the appearance of this oxidation product.
Article
Oncology
Masumi Hayazaki, Osamu Hatano, Saki Shimabayashi, Takumi Akiyama, Hiroshi Takemori, Akie Hamamoto
Summary: Zebrafish larvae were used to study leukoderma caused by RD, showing lightening of body color and decrease in melanophore numbers, as well as the production of black particles. RT-PCR analysis revealed significantly low mRNA levels of melanophore-specific genes and an increase in reactive oxygen species production in larvae treated with RD. These results indicate that zebrafish larvae could be used for evaluating leukoderma caused by chemicals, including RD.
PIGMENT CELL & MELANOMA RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Zhen Ren, Si Chen, Sery Pak, Lei Guo
Summary: Perhexiline induced cellular damage in primary human hepatocytes and HepG2 cells through ER stress-mediated apoptosis. Inhibition of ER stress attenuated the cytotoxicity of Perhexiline, while the p38 signaling pathway contributed to this process.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Dermatology
Yasuhiro Katahira, Eri Sakamoto, Aruma Watanabe, Yuma Furusaka, Shinya Inoue, Hideaki Hasegawa, Izuru Mizoguchi, Kazuyuki Yo, Fumiya Yamaji, Akemi Toyoda, Takayuki Yoshimoto
Summary: The tyrosinase inhibitor rhododendrol (RD), used as a skin whitening agent, has the potential to induce leukoderma. Through experiments, it was found that RD may enhance the expression of IL-12 in the human cell line activation test (h-CLAT) by metabolites that act on melanocytes. These findings contribute to predicting the sensitizing potential to induce leukoderma.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Article
Dermatology
Julia Dai, Robert S. Hight, Karina Grullon, Teresa L. Xiao, Sarah L. Stein
Summary: This article reports three cases of pediatric patients with vitiligo-like changes associated with GVHD, and reviews the literature on this topic. Improved understanding of this phenomenon may provide insights into the biological pathways of both vitiligo and GVHD.
PEDIATRIC DERMATOLOGY
(2023)
Review
Pharmacology & Pharmacy
Ankit Chaudhary, Mayank Patel, Shamsher Singh
Summary: Vitiligo is a chronic and progressive skin disorder characterized by the destruction of melanocytes, resulting in white patches on the skin. The disease has a relatively high prevalence and can be caused by various factors such as genetics, immune activation, and oxidative stress. Treatment options include topical medications and phototherapies.
CURRENT DRUG TARGETS
(2022)
Article
Medicine, Legal
Donald L. Bjerke, Shengde Wu, Kazumasa Wakamatsu, Shosuke Ito, Jiazhen Wang, Timothy Laughlin, Tomohiro Hakozaki
Summary: A framework is proposed to evaluate the risk of chemical leukoderma caused by specific compounds using physical and chemical characteristics, structure-activity relationship, and predictive metabolism tools. In vitro and in vivo tests are employed to assess the risk. Various cosmetic ingredients are evaluated using this framework.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Paolo Custurone, Luca Di Bartolomeo, Natasha Irrera, Francesco Borgia, Domenica Altavilla, Alessandra Bitto, Giovanni Pallio, Francesco Squadrito, Mario Vaccaro
Summary: Vitiligo is a chronic autoimmune dermatosis with limited understanding of its pathogenesis. Current research focuses on immune mediators and biological drugs to improve treatment outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Dermatology
K. S. Thomas, J. M. Batchelor, P. Akram, J. R. Chalmers, R. H. Haines, G. D. Meakin, L. Duley, J. C. Ravenscroft, A. Rogers, T. H. Sach, M. Santer, W. Tan, J. White, M. E. Whitton, H. C. Williams, S. T. Cheung, H. Hamad, A. Wright, J. R. Ingram, N. J. Levell, J. M. R. Goulding, A. Makrygeorgou, A. Bewley, M. Ogboli, J. Stainforth, A. Ferguson, B. Laguda, S. Wahie, R. Ellis, J. Azad, A. Rajasekaran, V. Eleftheriadou, A. A. Montgomery
Summary: For localized vitiligo, combination treatment with home-based handheld NB-UVB plus TCS is more effective than TCS alone, but successful in only around one-quarter of participants; participants with higher adherence during treatment were more likely to achieve treatment success, but the effects were lost once treatment stopped; combination treatment was relatively safe and well tolerated.
BRITISH JOURNAL OF DERMATOLOGY
(2021)
Article
Oncology
Sofia Verkhovskaia, Francesca Romana Di Pietro, Simona Mastroeni, Maria Luigia Carbone, Damiano Abeni, Roberto Morese, Francesca Maria Morelli, Stefania D'Atri, Paolo Marchetti, Federica De Galitiis, Cristina Maria Failla, Cristina Fortes
Summary: The study found that the onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome and an independent predictor factor for longer duration of clinical benefits in patients treated with immune checkpoint inhibitors.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ping He, Olivia Mann-Collura, Jacob Fling, Naga Edara, Rebecca Hetz, Mohammed S. Razzaque
Summary: High extracellular phosphate levels can lead to diverse cellular toxicity, including promoting cell proliferation, causing cell damage, and inducing apoptosis. Elevated phosphate activates AKT and MAPK pathways, resulting in epithelial-mesenchymal transition and ER stress. Inhibiting phosphate transport or interfering with signaling pathways can reduce phosphate-induced cytotoxicity.
Article
Biochemistry & Molecular Biology
Takahiro Oyama, Haruka Ogawa, Yoko Shirai, Hideaki Abe, Takanori Kamiya, Takehiko Abe, Sei-ichi Tanuma
Summary: The natural compound hinokitiol has been found to inhibit the activity of the key enzyme tyrosinase (TYR) involved in melanin production. This study investigated the mechanisms by which hinokitiol decreases intracellular levels of TYR and the transcription factor MITF. The findings suggest that hinokitiol induces endoplasmic reticulum (ER) stress and triggers the degradation of TYR and MITF through the ER-associated protein degradation (ERAD) pathway.
Article
Oncology
Masatoshi Kondo, Keigo Kawabata, Kohji Sato, Sayuri Yamaguchi, Akira Hachiya, Yoshito Takahashi, Shintaro Inoue
PIGMENT CELL & MELANOMA RESEARCH
(2016)
Article
Neurosciences
Yuta Yoshino, Mitsue Ishisaka, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hiroyuki Yoshida, Shintaro Inoue, Masayuki Shimoda, Yasunori Okada, Hideaki Hara
Article
Biochemistry & Molecular Biology
Yuta Yoshino, Masamitsu Shimazawa, Shinsuke Nakamura, Shintaro Inoue, Hiroyuki Yoshida, Masayuki Shimoda, Yasunori Okada, Hideaki Hara
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Article
Biochemistry & Molecular Biology
Yuta Yoshino, Masakazu Goto, Hideaki Hara, Shintaro Inoue
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Article
Multidisciplinary Sciences
Kazal Boron Biswas, Aya Takahashi, Yukiko Mizutani, Satoru Takayama, Asako Ishitsuka, Lingli Yang, Fei Yang, Arunasiri Iddamalgoda, Ichiro Katayama, Shintaro Inoue
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Shinya Sato, Yukiko Mizutani, Yuta Yoshino, Manami Masuda, Megumi Miyazaki, Hideaki Hara, Shintaro Inoue
Summary: The study showed that a mixture of pro-inflammatory cytokines negatively regulates hyaluronan (HA) metabolism in skin by suppressing HYBID and promoting HAS2, with HA synthesis mainly driven by IL-1 beta.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Dermatology
Kayoko Matsunaga, Kayoko Suzuki, Akiko Ito, Atsushi Tanemura, Yuko Abe, Tamio Suzuki, Momoko Yoshikawa, Yasuyuki Sumikawa, Akiko Yagami, Yukiko Masui, Shintaro Inoue, Shosuke Ito, Ichiro Katayama
Summary: The study found that the use of skin-whitening cosmetics containing rhododendrol may increase the risk of leukoderma, with ultraviolet light therapy being the most effective treatment. Oral vitamin D3 and a topical prostaglandin derivative have also been reported to be effective in treating rhododendrol-induced leukoderma.
JOURNAL OF DERMATOLOGY
(2021)
Review
Dermatology
Shintaro Inoue, Ichiro Katayama, Tamio Suzuki, Atsushi Tanemura, Shosuke Ito, Yuko Abe, Yasuyuki Sumikawa, Momoko Yoshikawa, Kayoko Suzuki, Akiko Yagami, Yukiko Masui, Akiko Ito, Kayoko Matsunaga
Summary: This review examines the major considerations for developing rhododendrol-induced leukoderma, providing a wide range of information on pathophysiology, mechanisms, risk evaluation, and potential treatments. The review discusses cytotoxicity of rhododendrol, cytoprotective functions, involvement of the immune system, and potential novel treatments, addressing individual differences and the mechanisms underlying the condition. Understanding rhododendrol-induced leukoderma not only sheds light on the mechanisms of non-segmental vitiligo, but also suggests possible prevention and treatment strategies.
JOURNAL OF DERMATOLOGY
(2021)
Article
Neurosciences
Shohei Tsuji, Shinsuke Nakamura, Tetsuya Yamada, Susana de Vega, Yasunori Okada, Shintaro Inoue, Masamitsu Shimazawa, Hideaki Hara
Summary: The study highlights the significant role of hyaluronan binding protein in glioblastoma, with its deficiency inhibiting cell proliferation and migration, and increasing cell death. Mouse experiments also confirmed these findings, suggesting potential therapeutic targets in the tumor microenvironment of glioblastoma.
Article
Dermatology
Yukiko Mizutani, Nao Takagi, Haruna Nagata, Shintaro Inoue
Summary: The study revealed that IFN-gamma inhibits claudin-1 expression leading to TJ dysfunction, while IL-17A can restore IFN-gamma-induced TJ dysfunction by activating atypical protein kinase C zeta instead of recovering TJ protein expression. These findings provide insights for personalized AD treatment using systemic therapies with anti-cytokine antibodies and/or JAK inhibitors.
EXPERIMENTAL DERMATOLOGY
(2021)
Letter
Dermatology
Haruna Nagata, Nao Takagi, Shintaro Inoue, Yukiko Mizutani
JOURNAL OF DERMATOLOGICAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Qianqian Wang, Yasutaka Kuroda, Lingli Yang, Sylvia Lai, Yukiko Mizutani, Arunasiri Iddamalgoda, Jiao Guo, Asako Yamamoto, Daiki Murase, Yoshito Takahashi, Leihong Xiang, Shintaro Inoue, Daisuke Tsuruta, Ichiro Katayama
Summary: Glycoprotein non-metastatic melanoma protein B (GPNMB) is an important transmembrane glycoprotein involved in cancer metastasis and osteoblast differentiation, with protective effects on melanocytes from oxidative stress. Decreased GPNMB expression was observed in vitiligo and rhododendrol-induced leukoderma, suggesting a potential role in their pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Masashi Mikami, Ohba Takuya, Yuta Yoshino, Shinsuke Nakamura, Kenichi Ito, Hiroyuki Kojima, Tatsuji Takahashi, Arunasiri Iddamalgoda, Shintaro Inoue, Masamitsu Shimazawa, Hideaki Hara
Summary: Acorus calamus extract and alpha-asarone demonstrate protective effects against oxidative stress and ER stress in hippocampal cells by reducing ROS production and inhibiting PERK signaling. Alpha-asarone shows potential as a therapeutic candidate for neurodegenerative diseases, including Alzheimer's disease.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2021)
Article
Pathology
Masayuki Shimoda, Hiroyuki Yoshida, Sakiko Mizuno, Toru Hirozane, Keisuke Horiuchi, Yuta Yoshino, Hideaki Hara, Yae Kanai, Shintaro Inoue, Muneaki Ishijima, Yasunori Okada
AMERICAN JOURNAL OF PATHOLOGY
(2017)
Meeting Abstract
Clinical Neurology
Yuta Yoshino, Mitsue Ishisaka, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hiroyuki Yoshida, Shintaro Inoue, Masayuki Shimoda, Yasunori Okada, Hideaki Hara
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2016)