B12, Folsäure
Gingko Bil.
Freie Radikale
Biochemische Flußdiagramme

Role of antioxidants in the survival of normal and vitiliginous avian melanocytes.
Cell Mol Biol (Noisy-le-grand) 1999 Nov;45(7):1065-74    (ISSN: 0145-5680)
Bowers RR; Nguyen B; Buckner S; Gonzalez Y; Ruiz F
Department of Biology and Microbiology, California State University, Los Angeles, 90032, USA. rbowers@calstatela.edu.
Mutant feather melanocytes from Barred Plymouth Rock (BPR) and White Leghorn (WL) chickens are currently being used as avian models of vitiligo. Feather melanocytes in BPR and WL chickens die prematurely in vivo due to low (50-66%) antioxidant glutathione and superoxide dismutase levels when compared to the wild type Jungle Fowl (JF) melanocytes. Excess superoxide anions, generated by xanthine:xanthine oxidase (X:XO), caused a 15-20% increase in mortality after 1 and 2 hrs. in all three genotypes of in vitro melanocytes as compared to control values that received no X:XO. Overall, the JF wild type melanocytes had the lowest mortality rate, WL melanocytes had the highest mortality rate and the BPR melanocytes had an intermediate mortality rate. Superoxide anion and hydroxyl radical production in the WL feather were double the production in the JF wild type feather. The production of reactive oxygen species in BPR was intermediate to the other two genotypes. In an effort to mimic the low antioxidant levels of the BPR and WL feathers in the JF feather, JF in vitro feather melanocytes were treated with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor. With BSO added to the medium, the JF mortality rates increased by 20-25%, reaching the mortality levels of the mutant BPR melanocytes. The addition of iron to the JF melanocyte X:XO medium increased their mortality rate by 20%, probably via the Fenton reaction. Thus, antioxidants play an extremely important role in both the viability of normal avian melanocytes and the premature death of the vitiliginous avian melanocytes. A working hypothesis, supported in part by the current results, is that the premature death of the mutant melanocytes could be precipitated in the poorly vascularized feather by low antioxidant protection due to both low turnover of tissue fluids which contain SOD and to genetically determined low levels of internal antioxidant protection in these melanocytes. This same mechanistic hypothesis could apply as "a" cause of premature melanocyte cell death in human vitiligo wherein the vitiliginous melanocytes may have a genetic defect in their antioxidant protection system and blood flow to an area may be restricted.

Alterations of mitochondria in peripheral blood mononuclear cells of vitiligo patients.
Pigment Cell Res 2003 Oct;16(5):553-9    (ISSN: 0893-5785)
Dell'Anna ML; Urbanelli S; Mastrofrancesco A; Camera E; Iacovelli P; Leone G; Manini P; D'Ischia M; Picardo M
Laboratorio di Fisiopatologia Cutanea, Istituto Dermatologico San Gallicano (IRCCS), Rome, Italy.
The possible role for a defective mitochondrial functionality in the pathogenesis of vitiligo was investigated by measuring intracellular levels of reactive oxygen species and of antioxidants, the activity of Krebs cycle enzymes, as well as the effects of inhibitors of the electron transport chain, in peripheral blood mononuclear cells from patients with active or stable disease vs. normal subjects. Plasma glyoxal levels were also determined in the same groups of subjects as an index of systemic oxidative stress. In patients with vitiligo in active phase, we observed an increased intracellular production of reactive oxygen species with a consequent imbalance of the prooxidant/antioxidant equilibrium, whereas plasma did not show apparent alterations in glyoxal levels, ruling out a systemic oxidative stress. In patients with stable disease, the balance between pro-oxidants and anti-oxidants seems to be maintained. Moreover, a marked increase in the expression of mitochondrial malate dehydrogenase activity and a specific sensitivity to electron transport chain complex I inhibitor were observed. Overall, these data provide further evidence for an altered mitochondrial functionality in vitiligo patients.

Epidermal oxidative stress in vitiligo.
Pigment Cell Res 1998 Apr;11(2):81-5    (ISSN: 0893-5785)
Passi S; Grandinetti M; Maggio F; Stancato A; De Luca C
Centro Invecchiamento Cellulare, Istituto Dermopatico dell'Immacolata (IRCCS), Roma, Italy.
Epidermal levels of enzymatic and non-enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), vitamin E (Vit E), ubiquinol (CoQ10H2), and reduced glutathione (GSH), as well as polyunsaturated fatty acids of phospholipids (PL-PUFA), were evaluated in the affected epidermis of 15 patients with active vitiligo (AVP) and in the corresponding epidermis of 15 healthy phototype matched controls. The epidermal levels of CoQ10H2, Vit E, GSH, and CAT activity were significantly reduced in AVP and were associated with a marked increase of oxidized glutathione, whereas SODs and GSH-Px activities and ubiquinone concentration remained similar to control values. Antioxidant deficiency, in particular the decline of lipophilic antioxidants, i.e., CoQ10H2 and Vit E, accounts well for PL-PUFA reduction observed in vitiligo epidermis, mainly affecting C18:3 n-3, C20:3 n-6, C20:4 n-6, and C22:6 n-3 fatty acids and suggesting the occurrence of a lipoperoxidative process. In conclusion, both an imbalance of the intracellular redox status and a significant depletion of enzymatic and non-enzymatic antioxidants feature the epidermis of AVP, and represent a fingerprint of an abnormal oxidative stress leading to epidermal cell injury.

Study on the antioxidant status of vitiligo patients of different age groups in baroda [In Process Citation]
Pigment Cell Res 2004 Jun;17(3):289-94    (ISSN: 0893-5785)
Agrawal D; Shajil EM; Marfatia YS; Begum R
Department of Biochemistry, Faculty of Science, M.S. University of Baroda, Vadodara, Gujarat, India.
One of the major hypotheses in the pathogenesis of vitiligo is the oxidative stress hypothesis. Pollution plays a major role in the production of free radicals. Gujarat, a highly industrialized state in India has a high prevalence of vitiligo patients. No previous studies were done on the age-dependent antioxidant status of vitiligo patients in Baroda city, Gujarat. Blood samples were collected from vitiligo patients of different age groups (5-15, 16-25, 26-35, 36-45 yr) and from age matched healthy volunteers. Antioxidant enzymes in blood such as catalase, superoxide dismutase, glutathione peroxidase and non-enzymatic antioxidants such as reduced glutathione and plasma vitamin E were estimated. Lipid peroxidation levels in erythrocytes and the reducing equivalent system, i.e. glucose-6-phosphate dehydrogenase were also measured. Significant increase in superoxide dismutase activity and lipid peroxidation levels in erythrocytes was observed in all age groups of vitiligo patients as compared with age-matched healthy controls, wherein an increase of 55% (P < 0.02) was observed in superoxide dismutase activity and lipid peroxidation levels in 36-45 yr age group. Whole blood glutathione levels, erythrocyte glutathione peroxidase and glucose-6-phosphate dehydrogenase activity were decreased significantly, whereas erythrocyte catalase activity and plasma vitamin E levels were not different in vitiligo patients as compared with age-matched healthy controls. No specific age group showed a significant difference. This is the first report on the age-dependent antioxidant status of vitiligo patients in Baroda. The disease affects individuals of any age group as shown in this study and systemic oxidative stress might precipitate the pathogenesis of vitiligo in susceptible patients.

Oxidant-antioxidant enzymes and lipid peroxidation in generalized vitiligo.
Clin Exp Dermatol 2004 Jul;29(4):406-9    (ISSN: 0307-6938)
Koca R; Armutcu F; Altinyazar HC; Gurel A
Department of Dermatology, Zonguldak Karaelmas University, Faculty of Medicine, Zonguldak, Turkey. rafkoca@yahoo.com.
Vitiligo is a common pigmentary disorder of the skin with selective destruction of melanocytes. The pathogenetic mechanisms in vitiligo have not been completely clarified. The aim of our investigation was to evaluate the oxidative stress in the pathogenesis of generalized vitiligo. Twenty-seven patients with generalized vitiligo and 24 phototype-, age-, and sex-matched healthy controls were included in this study. We analysed serum levels of malondialdehyde (MDA), nitric oxide (NO), and serum activities of superoxide dismutase (SOD) and xanthine oxidase (XO) in the patients with vitiligo and in the controls. We found significantly higher levels of MDA and XO activity (P < 0.001 and P < 0.05, respectively), and a significantly lower level of serum SOD activity (P < 0.05) in patients with vitiligo compared with the controls. However, the increase in the level of serum NO was insignificant (P > 0.05). These results suggest that lipid peroxidation of cellular membrane of melanocytes by free radicals may have a significant role in the pathogenesis of generalized vitiligo.