title: A novel role of topical iodine in skin: Activation of the Nrf2 pathway.
abstract: For a long time iodine has been used as an active dermal agent in the treatment of inflammatory, immune-mediated and infectious diseases. Moreover, topical iodine application has been reported to provide protection against sulfur-mustard-induced skin lesions, heat-induced and acid-induced skin burns in both haired guinea-pigs and mouse ear swelling models. However, the exact mechanism of action underlying these benefits of iodine has not yet been elucidated. In the current study, a novel mechanism of action by which iodine provides skin protection and relief, based on its electrophilic nature, is suggested. This study demonstrates that both iodine and iodide are capable of activating the Nrf2 pathway in human skin. As a result, skin protection against UVB-induced damage was acquired and the secretion of pro-inflammatory cytokines (IL-6, IL-8) from LPS-challenged skin was reduced. Iodide role in the enhanced activation of this pathway is demonstrated. The mode of action by which iodine and iodide activate the Nrf2 pathway is discussed.
authors.affiliation: The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 9112100, Israel; Department of Chemical Engineering, Technion-Israel Institute of Technology, Technion City, Haifa 3200003, Israel; The Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 32000, Israel; Department of Developmental Biology and Cancer Research, The Hebrew University Medical School, Ein-Karem Campus, Jerusalem 9112100, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Ben-Yehuda Greenwald
authors.affiliation: The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 9112100, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Frušić-Zlotkin
authors.affiliation: The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 9112100, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Soroka
authors.affiliation: Department of Developmental Biology and Cancer Research, The Hebrew University Medical School, Ein-Karem Campus, Jerusalem 9112100, Israel.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Ben-Sasson
authors.affiliation: Department of Chemical Engineering, Technion-Israel Institute of Technology, Technion City, Haifa 3200003, Israel; The Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Havazelet
authors.initials: H
authors.lastname: Bianco-Peled
authors.affiliation: The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 9112100, Israel. Electronic address: ronk@ekmd.huji.ac.il.
authors.forename: Ron
authors.initials: R
authors.lastname: Kohen
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D007454:Iodides / Q000008:administration & dosage; D007455:Iodine / Q000008:administration & dosage*; D051379:Mice; D009151:Mustard Gas / Q000633:toxicity; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D007454:Iodides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D007455:Iodine; D009151:Mustard Gas
keywords: Electrophiles; Iodine; Nrf2; Oxidants; Oxidative stress; Phase-II enzymes; Potassium iodide; Skin