Increased Sensitivity to Peroxidative Agents as a Possible Pathogenic Factor of Melanocyte Damage in Vitiligo

Abstract

To examine the sensitivity of vitiligo melanocytes to external oxidative stress, we studied enzymatic and non-enzymatic anti-oxidants in cultured melanocytes of normal subjects (n = 20) and melanocytes from apparently normal skin of vitiligo patients (n = 10). The activity of superoxide dismutase and catalase and the intracellular concentrations of vitamin E and ubiquinone were evaluated in cultures at the fourth or fifth passage. In addition, cells were exposed to various concentrations of a peroxidizing agent, cumene hydroperoxide (CUH, 0.66-20 microM), for 1 and 24 h. Compared to normal melanocytes, vitiligo melanocytes showed normal superoxide dismutase and significantly lower catalase activities and higher vitamin E and lower ubiquinone levels. At the concentration used, CUH did not significantly affect cell number or viability of melanocytes after either period of culture. On the contrary, vitiligo melanocytes were susceptible to the toxic effect of CUH after 24 h of continuous treatment at concentrations greater than 6.6 microM. The degree of CUH toxicity correlated strictly with the anti-oxidant pattern, defined as the ratio between vitamin E concentration and catalase activity, suggesting that the alteration in the antioxidants was the basis for sensitivity to the external oxidative stress. Our results demonstrate the presence of an imbalance in the anti-oxidant system in vitiligo melanocytes and provide further support for a free radical-mediated damage as an initial pathogenic event in melanocyte degeneration in vitiligo.

A Critical Appraisal of Vitiligo Etiologic Theories. Is Melanocyte Loss a Melanocytorrhagy?

“…The vacuolation and degenerative changes noted in NSV skin could be the expression of oxidative damage (51,52). Low catalase activity leading to epidermal accumulation of H 2 O 2 has been demonstrated in non-lesional and in lesional NSV skin (53) and in cultured melanocytes (54,55). Accumulation of H 2 O 2 in NSV skin in vivo has been shown (56).…”

Melanocytes and Oxidative Stress

“…However, the early death of vitiligo melanocytes was shown to be provoked by their increased sensitivity to oxidative stress, impacting tyrosinase activity and eumelanin synthesis [51,52]. It was also demonstrated that there were very high levels of H 2 O 2 and concomitant reduced activity of catalase in the epidermis of patients with vitiligo [53], reducing the levels of methionine sulfoxide reductase A and B and thioredoxin/thioredoxin reductase which triggers oxidative stress, As it was seen, during the process of melanogenesis, oxidative insults responsible for melanocyte damage can be caused not only by various ROS, namely H 2 O 2 , hydroxyl radicals and superoxide anion, but also by intermediates in melanin synthesis.…”

Quercetin attenuates the effects of H2O2 on endoplasmic reticulum morphology and tyrosinase export from the endoplasmic reticulum in melanocytes

“…The absence of melanocytes in the skin lesions was previously reported to be the key event in the pathogenesis of vitiligo (2); however, the aetiology of vitiligo remains to be elucidated. Previous studies have suggested that oxidative stress may result in the loss of melanocytes (3,4); increased intracellular reactive oxygen species (ROS) production was observed in the epidermis of vitiligo patients (5), which therefore indicates the presences of systemic oxidative stress in vitiligo (6,7). Accumulated oxidative stress leads to DNA damage, lipid and protein peroxidation and cell death (8,9).…”