{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:22:05Z","timestamp":1788870125379,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,6,27]],"date-time":"2014-06-27T00:00:00Z","timestamp":1403827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS)","award":["23591659, 26461705"],"award-info":[{"award-number":["23591659, 26461705"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2014,9]]},"abstract":"Summary<\/jats:title>\n \n \n RS<\/jats:styled-content>\n <\/jats:italic>\n \u20104\u2010(4\u2010Hydroxyphenyl)\u20102\u2010butanol (rhododendrol,\n RD<\/jats:styled-content>\n ) was used as a skin\u2010whitening agent until it was reported to induce leukoderma in July 2013. To explore the mechanism underlying its melanocyte toxicity, we characterized the tyrosinase\u2010catalyzed oxidation of\n RD<\/jats:styled-content>\n using spectrophotometry and\n HPLC<\/jats:styled-content>\n . Oxidation of\n RD<\/jats:styled-content>\n with mushroom tyrosinase rapidly produced\n RD<\/jats:styled-content>\n \u2010quinone, which was quickly converted to 2\u2010methylchromane\u20106,7\u2010dione (\n RD<\/jats:styled-content>\n \u2010cyclic quinone) and\n RD<\/jats:styled-content>\n \u2010hydroxy\u2010\n p<\/jats:italic>\n \u2010quinone through cyclization and addition of water molecule, respectively.\n RD<\/jats:styled-content>\n \u2010quinone and\n RD<\/jats:styled-content>\n \u2010cyclic quinone were identified as\n RD<\/jats:styled-content>\n \u2010catechol and\n RD<\/jats:styled-content>\n \u2010cyclic catechol after Na\n BH<\/jats:styled-content>\n 4<\/jats:sub>\n reduction. Autoxidation of\n RD<\/jats:styled-content>\n \u2010cyclic catechol produced superoxide radical.\n RD<\/jats:styled-content>\n \u2010quinone and\n RD<\/jats:styled-content>\n \u2010cyclic quinone quantitatively bound to thiols such as cysteine and\n GSH<\/jats:styled-content>\n . These results suggest that the melanocyte toxicity of\n RD<\/jats:styled-content>\n is caused by its tyrosinase\u2010catalyzed oxidation through production of\n RD<\/jats:styled-content>\n \u2010cyclic quinone which depletes cytosolic\n GSH<\/jats:styled-content>\n and then binds to essential cellular proteins through their sulfhydryl groups. The production of\n ROS<\/jats:styled-content>\n through autoxidation of\n RD<\/jats:styled-content>\n \u2010cyclic catechol may augment the toxicity.\n <\/jats:p>","DOI":"10.1111\/pcmr.12275","type":"journal-article","created":{"date-parts":[[2014,6,5]],"date-time":"2014-06-05T10:48:35Z","timestamp":1401965315000},"page":"744-753","source":"Crossref","is-referenced-by-count":71,"title":["Tyrosinase\u2010catalyzed oxidation of rhododendrol produces 2\u2010methylchromane\u20106,7\u2010dione, the putative ultimate toxic metabolite: implications for melanocyte toxicity"],"prefix":"10.1111","volume":"27","author":[{"given":"Shosuke","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Chemistry Fujita Health University School of Health Sciences Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ojika","sequence":"additional","affiliation":[{"name":"Department of Applied Molecular Biosciences Graduate School of Bioagricultural Sciences Nagoya University Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiharu","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Dermatology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Wakamatsu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Fujita Health University School of Health Sciences Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.29.1970"},{"key":"e_1_2_7_3_1","first-page":"3743","article-title":"Melanocytotoxicity and antimelanoma effects of phenolic amine compounds in mice in vivo","volume":"50","author":"Alena F.","year":"1990","journal-title":"Cancer Res."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.249532"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4686(85)80051-7"},{"key":"e_1_2_7_6_1","volume-title":"Biochemistry","author":"Berg J.M.","year":"2006"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1529-8019.2001.014001029.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx9902082"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.16"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.42.26226"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2005.10.055"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/S0026-895X(25)13536-0","article-title":"Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6\u2010hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro","volume":"14","author":"Graham D.G.","year":"1978","journal-title":"Mol. 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