title: Flavonols Protect Against UV Radiation-Induced Thymine Dimer Formation in an Artificial Skin Mimic.
abstract: OBJECTIVE
  Exposure of skin to ultraviolet light has been shown to have a number of deleterious effects including photoaging, photoimmunosuppression and photoinduced DNA damage which can lead to the development of skin cancer. In this paper we present a study on the ability of three flavonols to protect EpiDerm™, an artificial skin mimic, against UV-induced damage.
  
  
  METHODS
  EpiDerm™ samples were treated with flavonol in acetone and exposed to UVA (100 kJ/m(2) at 365 nm) and UVB (9000 J/m(2) at 310 nm) radiation. Secretion of matrix metalloproteinase-1 (MMP-1) and tumor necrosis factor-α (TNF-a) were determined by ELISA, cyclobutane pyrimidine dimers were quantified using LC-APCI-MS.
  
  
  RESULTS
  EpiDerm™ treated topically with quercetin significantly decreased MMP-1 secretion induced by UVA (100 µM) or UVB (200 µM) and TNF-a secretion was significantly reduced at 100 µM quercetin for both UVA and UVB radiation. In addition, topically applied quercetin was found to be photostable over the duration of the experiment. EpiDerm™ samples were treated topically with quercetin, kaempferol or galangin (52 µM) immediately prior to UVA or UVB exposure, and the cyclobutane thymine dimers (T-T (CPD)) were quantified using an HPLC-APCI MS/MS method. All three flavonols significantly decreased T-T (CPD) formation in UVB irradiated EpiDerm™, however no effect could be observed for the UVA irradiation experiments as thymine dimer formation was below the limit of quantitation.
  
  
  CONCLUSIONS
  Our results suggest that flavonols can provide protection against UV radiation-induced skin damage through both antioxidant activity and direct photo-absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
authors.affiliation: Drug Discovery and Development Research Group , College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Rd, Saskatoon, SK, Canada.
authors.forename: Sabia
authors.initials: S
authors.lastname: Maini
authors.forename: Brian M
authors.initials: BM
authors.lastname: Fahlman
authors.forename: Ed S
authors.initials: ES
authors.lastname: Krol
mesh_terms: D000279:Administration, Cutaneous; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D044948:Flavonols / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D044949:Kaempferols / Q000008:administration & dosage / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D010865:Pilot Projects; D011740:Pyrimidine Dimers / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D053719:Tandem Mass Spectrometry / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D005419:Flavonoids; D044948:Flavonols; D044949:Kaempferols; D011740:Pyrimidine Dimers; D014409:Tumor Necrosis Factor-alpha; C037032:galangin; C006552:kaempferol; D011794:Quercetin; D020781:Matrix Metalloproteinase 1