Presence of epidermal allantoin further supports oxidative stress in vitiligo

Shalbaf, Mohammad; Gibbons, Nicholas C. J.; Wood, John M.; Maitland, Derek J.; Rokos, Hartmut; Elwary, Souna M.; Marles, Lee K.; Schallreuter, Karin U.

doi:10.1111/j.1600-0625.2008.00697.x

Cited by 52 publications

(49 citation statements)

References 32 publications

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“…This augmented previous findings of increased H 2 O 2 , which were in vitro, based on cell culture and skin biopsies [63]. FT Raman spectroscopy also revealed oxidation of l-tryptophan in epidermal albumin, and HPLC showed the presence of allantoin in the epidermis, confirming the presence of oxidative stress in vitiligo [69,70]. Oxidative destruction of polyunsaturated fatty acids of phospholipids is referred to as lipid peroxidation.…”

Section: Ros In Vitiligosupporting

confidence: 82%

“…Nitric oxide synthases create H 2 O 2 in an environment deficient in l-arginine [77]. XO (xanthine oxidase) catalyses the conversion of purine bases into uric acid, and generates H 2 O 2 as a by-product [70]. Oxidation of aromatic phenols like 17β-oestradiol to catechols by an NADPH-dependent CYP (cytochrome P450) yields superoxide anion, which disproportionates to H 2 O 2 ; this diffuses into the epidermis [78].…”

Section: Sources Of Epidermal H 2 Omentioning

confidence: 99%

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Vitiligo, reactive oxygen species and T-cells

2010

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The acquired depigmenting disorder of vitiligo affects an estimated 1% of the world population and constitutes one of the commonest dermatoses. Although essentially asymptomatic, the psychosocial impact of vitiligo can be severe. The cause of vitiligo remains enigmatic, hampering efforts at successful therapy. The underlying pathogenesis of the pigment loss has, however, been clarified to some extent in recent years, offering the prospect of effective treatment, accurate prognosis and rational preventative strategies. Vitiligo occurs when functioning melanocytes disappear from the epidermis. A single dominant pathway is unlikely to account for all cases of melanocyte loss in vitiligo; rather, it is the result of complex interactions of biochemical, environmental and immunological events, in a permissive genetic milieu. ROS (reactive oxygen species) and H2O2 in excess can damage biological processes, and this situation has been documented in active vitiligo skin. Tyrosinase activity is impaired by excess H2O2 through oxidation of methionine residues in this key melanogenic enzyme. Mechanisms for repairing this oxidant damage are also damaged by H2O2, compounding the effect. Numerous proteins and peptides, in addition to tyrosinase, are similarly affected. It is possible that oxidant stress is the principal cause of vitiligo. However, there is also ample evidence of immunological phenomena in vitiligo, particularly in established chronic and progressive disease. Both innate and adaptive arms of the immune system are involved, with a dominant role for T-cells. Sensitized CD8+ T-cells are targeted to melanocyte differentiation antigens and destroy melanocytes either as the primary event in vitiligo or as a secondary promotive consequence. There is speculation on the interplay, if any, between ROS and the immune system in the pathogenesis of vitiligo. The present review focuses on the scientific evidence linking alterations in ROS and/or T-cells to vitiligo.

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Section: Ros In Vitiligosupporting

confidence: 82%

Section: Sources Of Epidermal H 2 Omentioning

confidence: 99%

Vitiligo, reactive oxygen species and T-cells

2010

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“…Altered cellular localization of Nrf2 in lesional vitiligo skin has also been reported (Guan et al, 2008a). Interestingly, vitiligo patients seem to exhibit systemic as well as localized oxidative stress (Passi et al, 1998;Rokos et al, 2002), and millimolar levels of H 2 O 2 are reported to be present in their epidermis (Schallreuter, 1999;Shalbaf et al, 2008). Several antioxidant proteins have been shown to be altered in patient groups (Ines et al, 2006;Arican and Kurutas, 2008), and metabolic changes in the skin induced by H 2 O 2 have also been reported (Schallreuter et al, 2006;Spencer et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Upregulation of Nrf2-Dependent Phase II Detoxification Genes in the Involved Epidermis of Vitiligo Vulgaris

Natarajan

Singh

Kumar

et al. 2010

Journal of Investigative Dermatology

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Oxidative stress is widely believed to be a contributing factor in vitiligo pathogenesis. To explore mechanisms by which epidermis responds to mounting oxidative stress, we investigated the involvement of phase II detoxification genes in vitiligo. Phase II detoxification pathways have recently been identified as being important in the regulation of epidermal skin homeostasis. In this study we show that the key transcription factor nuclear factor E2-related factor 2 (Nrf2) and the downstream genes NAD(P)H:quinone oxidase-1 (NQO-1), γ-glutamyl cystine ligase catalytic subunit (GCLC), and γ-glutamyl cystine ligase modifying subunit (GCLM) are upregulated in the lesional epidermal skin of subjects with vitiligo vulgaris. The differences between lesional and nonlesional skin were further investigated by studying the induced expression of Nrf2-dependent transcripts in skin punch biopsies using curcumin and santalol. Surprisingly, nonlesional skin showed induction of all transcripts while a similar effect was not observed for the skin punches from the lesional skin. The use of curcumin and santalol on epidermal cells showed that keratinocytes were more susceptible to apoptosis, whereas melanocytes induced phase II genes under the same concentrations with negligible apoptosis. Our studies provide new insights into the role of phase II detoxification pathway in maintaining skin homeostasis and sustaining redox balance in vitiligo patients.

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“…The overall decreased activities of BchE and AchE were apparent in both lesional and non-lesional skin of vitiligo patients demonstrating that the effects of H 2 O 2 occur throughout the entire epidermal compartment. Considering the previous research on H 2 O 2 accumulation in vitiligo, Shalbaf et al (2008) investigated xanthine oxidase (XO) as a source of H 2 O 2 because it produces H 2 O 2 in its reaction pathway. XO is found in many tissues and catalyzes the oxidative hydroxylation of hypoxanthine to xanthine and then xanthine to uric acid, which is accompanied by H 2 O 2 production (Mathews et al, 2000 as cited in Shalbaf et al, 2008).…”

Section: The Role Of Tetrahydrobiopterin Recycling and Other Indicatomentioning

confidence: 99%

“…Considering the previous research on H 2 O 2 accumulation in vitiligo, Shalbaf et al (2008) investigated xanthine oxidase (XO) as a source of H 2 O 2 because it produces H 2 O 2 in its reaction pathway. XO is found in many tissues and catalyzes the oxidative hydroxylation of hypoxanthine to xanthine and then xanthine to uric acid, which is accompanied by H 2 O 2 production (Mathews et al, 2000 as cited in Shalbaf et al, 2008). XO also oxidizes uric acid to allantoin, a substance that acts a marker of oxidative stress (Benzie et al, 1999).…”

Section: The Role Of Tetrahydrobiopterin Recycling and Other Indicatomentioning

confidence: 99%