In Vivo and In Vitro Evidence for Hydrogen Peroxide (H2O2) Accumulation in the Epidermis of Patients with Vitiligo and its Successful Removal by a UVB-Activated Pseudocatalase

Abstract

To date there is compelling in vitro and in vivo evidence for epidermal H2O2 accumulation in vitiligo. This paper reviews the literature and presents new data on oxidative stress in the epidermal compartment of this disorder. Elevated H2O2 levels can be demonstrated in vivo in patients compared with healthy controls by utilizing Fourier-Transform Raman spectroscopy. H2O2 accumulation is associated with low epidermal catalase levels. So far, four potential sources for epidermal H2O2 generation in vitiligo have been identified: (i) perturbed (6R)-L-erythro 5,6,7,8 tetrahydrobiopterin (6BH4) de novo synthesis/recycling/regulation; (ii) impaired catecholamine synthesis with increased monoamine oxidase A activities; (iii) low glutathione peroxidase activities; and (iv) "oxygen burst" via NADPH oxidase from a cellular infiltrate. H2O2 overproduction can cause inactivation of catalase as well as vacuolation in epidermal melanocytes and keratinocytes. Vacuolation was also observed in vitro in melanocytes established from lesional and nonlesional epidermis of patients (n = 10) but was reversible upon addition of catalase. H2O2 can directly oxidize 6BH4 to 6-biopterin, which is cytotoxic to melanocytes in vitro. Therefore, we substituted the impaired catalase with a "pseudocatalase". Pseudocatalase is a bis-manganese III-EDTA-(HCO3-)2 complex activated by UVB or natural sun. This complex has been used in a pilot study on 33 patients, showing remarkable repigmentation even in long lasting disease. Currently this approach is under worldwide clinical investigation in an open trial. In conclusion, there are several lines of evidence that the entire epidermis of patients with vitiligo is involved in the disease process and that correction of the epidermal redox status is mandatory for repigmentation.

Age-related Accumulation of Non-heme Ferric and Ferrous Iron in Mouse Ovarian Stroma Visualized by Sensitive Non-heme Iron Histochemistry

“…In humans, oxidative damage of oocytes and granulosa cells was described in the cohort of primordial follicles in women of advanced age (de Bruin et al 2004). ROS perturb the microenvironment in and around ova and granulosa cells and decrease the viability of oocytes and embryos (Miyamoto et al 2010;Van Blerkom et al 1997;Yang et al 1998;Schallreuter et al 1999). By contrast, it has been also demonstrated that ROS, including superoxide and hydrogen peroxide, play critical roles in the regulation of ovarian functions, such as oocyte maturation, folliculogenesis, ovarian steroidogenesis, and luteolysis.…”

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

“…Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182] …”

“…In fact, despite extensive data in the literature implicating a role for ROS and oxidative stress in many chronic diseases, such as cardiovascular disease, diabetes, cancer, and kidney disease, there are very few clinical conditions that are directly due to altered ROS levels. These include vitiligo, neurodegenerative diseases, and progeria (67,99,117,145,172,216). With regard to clinical hypertension, most studies examining ROS are based on associations between plasma or urine markers of oxidative stress and blood pressure.…”

High Dissociation Rate Constant of Ferrous-Dioxy Complex Linked to the Catalase-like Activity in Lactoperoxidase

“…Hydrogen peroxide (H 2 O 2 ) is freely diffusible through biological membranes, and its overproduction or inhalation is extremely destructive to cells and tissues (1,2). Superoxide (O 2 .…”