title: Oral zinc sulphate causes murine hair hypopigmentation and is a potent inhibitor of eumelanogenesis in vivo.
abstract: BACKGROUND
  C57BL/6 a/a mice have been widely used to study melanogenesis, including in electron paramagnetic resonance (EPR) studies. Zinc cations modulate melanogenesis, but the net effect of Zn2+ in vivo is unclear, as the reported effects of Zn2+ on melanogenesis are ambiguous: zinc inhibits tyrosinase and glutathione reductase in vitro, but also enhances the activity of dopachrome tautomerase (tyrosinase-related protein-2) and has agonistic effects on melanocortin receptor signalling.
  
  
  OBJECTIVE
  To determine in a C57BL/6 a/a murine pilot study whether excess zinc ions inhibit, enhance or in any other way alter hair follicle melanogenesis in vivo, and to test the usefulness of EPR for this study.
  
  
  METHODS
  ZnSO(4).7H2O was continuously administered orally to C57BL/6 a/a mice during spontaneous and depilation-induced hair follicle cycling (20 mg mL-1; in drinking water; mean+/-SD daily dose 1.2+/-0.53 mL), and hair pigmentation was examined macroscopically, by routine histology and by EPR.
  
  
  RESULTS
  Oral zinc cations induced a bright brown lightening of new hair shafts produced during anagen, but without inducing an EPR-detectable switch from eumelanogenesis to phaeomelanogenesis. The total content of melanin in the skin and hair shafts during the subsequent telogen phase, i.e. after completion of a full hair cycle, was significantly reduced in Zn-treated mice (P=0.0005). Compared with controls, melanin granules in precortical hair matrix keratinocytes, hair bulb melanocytes and hair shafts of zinc-treated animals were reduced and poorly pigmented. Over the course of several hair cycles, lasting hair shaft depigmentation was seen during long-term exposure to high-dose oral Zn2+.
  
  
  CONCLUSIONS
  High-dose oral Zn2+ is a potent downregulator of eumelanin content in murine hair shafts in vivo. The C57BL/6 mouse model offers an excellent tool for further dissecting the as yet unclear underlying molecular basis of this phenomenon, while EPR technology is well suited for the rapid, qualitative and quantitative monitoring of hair pigmentation changes.
authors.affiliation: Department of Biophysics, Faculty of Biotechnology, Jagiellonian University, ul. Gronostajowa 7, PL-30-387 Krakow, Poland, and Department of Dermatology, University Hospital Schleswig-Holstein, Lübeck, Germany. mieszko@mol.uj.edu.pl
authors.forename: P M
authors.initials: PM
authors.lastname: Plonka
authors.forename: B
authors.initials: B
authors.lastname: Handjiski
authors.forename: D
authors.initials: D
authors.lastname: Michalczyk
authors.forename: M
authors.initials: M
authors.lastname: Popik
authors.forename: R
authors.initials: R
authors.lastname: Paus
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003879:Dermatologic Agents / Q000009:adverse effects*; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006197:Hair / Q000737:chemistry / Q000254:growth & development; D006200:Hair Color / Q000187:drug effects*; D017496:Hypopigmentation / Q000139:chemically induced*; D008543:Melanins / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D019287:Zinc Sulfate / Q000009:adverse effects*
chemical_list: D003879:Dermatologic Agents; D008543:Melanins; C041877:eumelanin; D019287:Zinc Sulfate