Estrogens Can Contribute to Hydrogen Peroxide Generation and Quinone-Mediated DNA Damage in Peripheral Blood Lymphocytes from Patients with Vitiligo

To date there is ample in vivo and in vitro evidence for increased epidermal and systemic hydrogen peroxide (H2O2) 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 H2O2 by oxidative metabolism of estrogens and other aromatic steroids was documented. Therefore, it was tempting to follow estrogen-generated H2O2 and its possible effect on DNA damage in peripheral blood lymphocytes from patients with vitiligo before and after the reduction of epidermal H2O2 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 labeling together with determination of basal H2O2 levels in peripheral blood lymphocytes. To test the influence of estrogen on H2O2 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 H2O2 leads to both increased epidermal catalase protein expression as well as decreased H2O2 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.