title: Estrogens can contribute to hydrogen peroxide generation and quinone-mediated DNA damage in peripheral blood lymphocytes from patients with vitiligo.
abstract: To date there is ample in vivo and in vitro evidence for increased epidermal and systemic hydrogen peroxide (H(2)O(2)) levels in vitiligo, which can be reduced with a topical application of a pseudocatalase-K.U. Schallreuter (PC-KUS) leading to the recovery of epidermal catalase levels as well as other enzymes in peripheral blood cells. Recently, the generation of H(2)O(2) by oxidative metabolism of estrogens and other aromatic steroids was documented. Therefore, it was tempting to follow estrogen-generated H(2)O(2) and its possible effect on DNA damage in peripheral blood lymphocytes from patients with vitiligo before and after the reduction of epidermal H(2)O(2) with pseudocatalase PC-KUS compared to controls. For this purpose, 20 Caucasian patients were grouped in treated responders (group A, n=11) and untreated active/acute disease (group B, n=9) and compared to Caucasian healthy controls (group C, n=7). Consequently, epidermal catalase protein expression in full skin biopsies was assessed using immunofluorescence labelling together with determination of basal H(2)O(2) levels in peripheral blood lymphocytes. To test the influence of estrogen on H(2)O(2) generation and DNA damage, freshly prepared peripheral blood lymphocytes from all three groups were used for the alkaline comet assay in the presence and absence of catalase. The results of this study demonstrated that reduction of epidermal H(2)O(2) leads to both increased epidermal catalase protein expression as well as decreased H(2)O(2) concentrations in lymphocytes. Moreover, a direct estrogen-mediated DNA damage was identified in both patient groups, which was absent in healthy controls. This effect was not abolished by catalase pointing to direct quinone-mediated DNA damage by estrogens in peripheral blood lymphocytes in vitiligo.
authors.affiliation: Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, Bradford BD7 1DP, UK. K.Schallreuter@bradford.ac.uk
authors.forename: Karin U
authors.initials: KU
authors.lastname: Schallreuter
authors.forename: Georgia
authors.initials: G
authors.lastname: Chiuchiarelli
authors.forename: Eduardo
authors.initials: E
authors.lastname: Cemeli
authors.forename: Souna M
authors.initials: SM
authors.lastname: Elwary
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Gillbro
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Spencer
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rokos
authors.forename: Angela
authors.initials: A
authors.lastname: Panske
authors.forename: Bhaven
authors.initials: B
authors.lastname: Chavan
authors.forename: John M
authors.initials: JM
authors.lastname: Wood
authors.forename: Diana
authors.initials: D
authors.lastname: Anderson
mesh_terms: D000328:Adult; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D004249:DNA Damage; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011809:Quinones / Q000633:toxicity*; D014820:Vitiligo / Q000378:metabolism*
chemical_list: D004967:Estrogens; D011809:Quinones; D006861:Hydrogen Peroxide; C038109:pseudocatalase; D002374:Catalase