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Abstract
Objectives: To evaluate the role of oxidative stress in the pathogenesis of vitiligo and the effect of
narrowband (NB) ultraviolet (UV) B phototherapy on oxidative stress markers.
Methods: Patients with vitiligo and healthy control subjects were included in the study. Patients in
the vitiligo group were treated with an NB-UVB regimen (3 weekly for 6 months). Erythrocyte
superoxide dismutase activity (SOD), erythrocyte malonyldialdehyde (MDA) and erythrocyte
glutathione peroxidase activity (GSH-Px) levels were assessed in all participants at baseline, and
after NB-UVB phototherapy in patients with vitiligo.
Results: A total of 24 patients with vitiligo and 27 control subjects were included in the study.
Before treatment, erythrocyte MDA levels were significantly higher, and SOD and GSH-Px levels
were significantly lower, in patients with vitiligo compared with controls. NB-UVB phototherapy
was associated with a significant reduction in MDA levels and a significant increase in GSH-Px
levels, compared with baseline, in patients with vitiligo.
Conclusion: NB-UVB phototherapy may relieve oxidative stress in patients with vitiligo by
reversing the oxidantantioxidant imbalance that is considered to play a role in the pathogenesis of
this disease.
Corresponding author:
Cenk Akcali, Dermatology Department, Medical School,
Gaziantep Universitesi Sahinbey Arastrma ve Uygulama
Hastanesi, Kilis yolu uzeri, 27010 Sahinbey Gaziantep,
Turkey.
Email: cenkakcali@gmail.com
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800
Keywords
Vitiligo, narrowband UVB phototherapy, oxidative stress, erythrocyte malonyldialdehyde,
erythrocyte glutathione peroxidase activity, GSH-Px, erythrocyte superoxide dismutase
Date received: 30 October 2013; accepted: 19 November 2013
Introduction
Vitiligo is characterized by the destruction
of melanocytes in the skin, resulting in the
appearance of well-circumscribed white
macules.1 The exact pathophysiological
mechanism of vitiligo remains elusive,2
which has therefore generated extensive
research into melanocyte biology and pigmentation disorders.3 As a worldwide disease with a prevalence of 2%, vitiligo is
considered to be a multifactorial and polygenic disease that is associated with the loss
of epidermal melanocytes; the condition is
proposed to be underlined by autoimmune,
biochemical, oxidantantioxidant, neural
and viral mechanisms, as well as genetic
susceptibility.4
While the pathogenesis of vitiligo remains
unclear, oxidative stress has been considered
to be one of the likely causative factors in the
initiation of the white skin patches of vitiligo,3
based on melanocyte destruction caused by
accumulation of toxic free radicals.4,5
The rst report conrming the use of
narrowband (NB) ultraviolet (UV) B phototherapy in patients with vitiligo was published in 1997.6,7 This indicated that a
wavelength of around 311 nm had a favourable safety prole and was clinically more
eective than full-spectrum UVB. Since
then, NB-UVB phototherapy has been
used as a rst-choice strategy for most
vitiligo patients,8 as an alternative to the
mainstay of treatment for generalized and
focal vitiligo, which utilizes psoralen plus
UVA (PUVA) photochemotherapy and topical corticosteroids (such an approach has
been used for many years).9
Narrowband-UVB has been reported to
be a good wavelength to which vitiligo
responds.10 Hence, because of the uncertainty concerning the role of oxidative stress
in the pathogenesis of vitiligo, as well as the
known mechanism of action of NB-UVB on
the condition,1,4,5 the present study was
designed to evaluate the role of oxidative
stress in the pathogenesis of vitiligo. This
was undertaken by investigating serum
alterations in oxidant (erythrocyte malonyldialdehyde; MDA) and antioxidant
(erythrocyte superoxide dismutase [SOD]
and erythrocyte glutathione peroxidase
[GSH-Px]) activity markers. Investigation
of the eect of NB-UVB phototherapy on
oxidative stress markers was the secondary
objective of the study.
Methods
Patients
Patients newly diagnosed with generalized
vitiligo on admission to the Dermatology
Department at Gaziantep University
Faculty of Medicine, Gaziantep, Turkey,
were recruited sequentially between
February 2009 and August 2009. Patients
had to be >12 and <68 years of age, with no
other skin disease. Control subjects were
enrolled from Gaziantep University hospital
workers and residency students, as well as
volunteers from the town of Gaziantep.
Control subjects (who were age- and sexmatched) did not show signs of active infection, were free of any other dermatological
disorder, were not using any other medications and did not use alcohol or smoke
cigarrettes.
Written informed consent was obtained
from every study participant following a
detailed explanation of the study objectives
and protocol. The study was conducted in
Karsli et al.
801
Biochemical analyses
Blood samples were taken twice from
patients with vitiligo (before and after
Statistical analyses
Data were presented as mean SD and/or
per cent. Analysis of continuous variables
was performed using Students t-test or
MannWhitney U-test, wheareas analysis of
categorical variables was performed using
2-test or Wilcoxons signed-rank test.
802
Results
A total of 27 patients with vitiligo (14 male)
and 27 healthy controls (15 male) were
included in the study. Patients with vitiligo
were 1467 years old. Two male patients
were excluded due to concomitant disease
(hepatitis B and diabetes mellitus) and one
female patient was excluded due to pregnancy, yielding a patient population of 24.
The vitiligo and control groups were
homogenous in terms of age and sex distribution, with equal numbers of female and
male patients (Table 1). There were no
concomitant autoimmune disorders in the
patients with vitiligo. Family history of
vitiligo was present in six men and ve
women.
Erythrocyte MDA levels in the vitiligo
group before treatment were signicantly
higher compared with levels observed in the
control group (P 0.001; Table 2). When
measurements taken in patients before and
after treatment were compared, NB-UVB
phototherapy was associated with signicantly reduced MDA levels (P 0.001), but
these were still markedly higher than the
Table 1. Patient demographics in healthy control subjects and patients with vitiligo at baseline,
in a study that evaluated the role of oxidative stress in the pathogenesis of vitiligo and the effect
of narrowband ultraviolet B phototherapy on oxidative stress markers.
Characteristic
Age, years
Sex
Female
Male
Control group
n 27
Vitiligo group
n 24
Total
32.2 12.8
34.9 16.7
33.49 13.2
12 (44.4)
15 (55.6)
12 (50.0)
12 (50.0)
24 (100.0)
27 (100.0)
Table 2. Mean erythrocyte superoxide dismutase activity (SOD), erythrocyte malonyldialdehyde (MDA),
and erythrocyte glutathione peroxidase activity (GSH-Px) levels in healthy controls, and in patients with
vitiligo (before and after 6 months narrowband ultraviolet-B therapy given 3 weekly).
Parameter
Control group
n 27
Vitiligo group
pretreatment n 24
Vitiligo group
post-treatment n 24
MDA, nmol/g Hb
SOD, U/mg Hb
GSH-Px, U/g Hb
32.57 7.59
2.46 0.48
18.87 4.42
43.31 8.62z
2.19 0.42*
13.71 3.85z
38.30 8.09*
2.20 0.58*
15.33 3.25y
Karsli et al.
803
Discussion
The precise pathogenesis of vitiligo has not
been claried, despite several proposed
theories that implicate the loss of epidermal
melanocytes as the main underlying factor in
this disorder.4 In this regard, oxidative stress
has been suggested as one of the aetiopathogenetic factors of vitiligo disease, triggering
melanocyte destruction14 resulting from
overproduction of reactive oxygen metabolites and/or limited production of antioxidants.15,16 Hence, patients with vitiligo have
been considered to be susceptible to higher
levels of oxidative stress than healthy
people, due to documented reductions in
erythrocyte glutathione levels, which are
known to prevent free radical-mediated
injury.17
Accordingly, the higher levels of MDA
but lower levels of SOD and GSH-Px seen
in patients in this study before NB-UVB
treatment seemed to indicate the remarkable
imbalance in the oxidantantioxidant
system among patients with vitiligo in
favour of oxidant mechanisms, which may
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Funding
This research received no specic grant from any
funding agency in the public, commercial, or notfor-prot sectors.
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