Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
The Role of Topical and Oral Melatonin in Management of Melasma
Patients
Salim A. Hamadi1, Mohammed Mahmmod Mohammed2, Ashwaq Nejmelden Aljaf3
& Ali Abdulrazak4
1
Faculty of pharmacy & Medical Sciences, Petra University, Amman, Jordan, 2 College of pharmacy,
University of Almustansiryah, Baghdad, Iraq, 3 College of pharmacy, University of Baghdad, Baghdad,
Iraq, 4 Alkarama teaching hospital, Baghdad, Iraq
Dr. Salim A. Hamadi, Faculty of pharmacy & Medical Sciences, Petra University,
P.O. Box: 961343, Amman, Jordan
E-mail: Hamadi_54@yahoo.com
ABSTRACT
This novel study was designed to evaluate the possible effects of topically formulated melatonin
cream alone or in combination with sunscreen and oral melatonin for the management of
melasma patients in comparison with hydroquinone as a standard therapy. This study carried out
in the dermatology department at the AL-Karama teaching hospital, Baghdad, Iraq. In a double
blind manner, this preliminary clinical study was performed on 36 patients with epidermal
melasma and 10 healthy subjects as control. They were diagnosed as having melasma and they
were under dermatologist supervision during the entire period of treatment. The patients were
allocated into four groups (A, B, C, and D), and treated with topical melatonin only, topical
melatonin and sunscreen, topical and oral melatonin, and 4% hydroquinone cream, respectively
for a period of 90 days followed by 30 days treatment with placebo. The severity of melasma was
evaluated using the Melasma Area & Severity Index (MASI) before starting treatment and after
each 15 days for 120 days. To evaluate the oxidative stress status, malondialdehyde (MDA) and
glutathione (GSH) levels in plasma were measured before starting treatment and after 45, 90,
and 120 days of treatment.
At the end of treatment period (90 days); all melasma patients demonstrated significant reduction
in MASI score in different levels. In addition, the plasma MDA levels were decreased and plasma
GSH levels were increased in different scales after 90 days of treatment. The overall results of
this preliminary study suggested that topical melatonin could be used as a hypopigmenting agent
in treatment of melasma, and this effect is augmented by the oral administration of the drug and
the use of sunscreen, possibly by its antioxidant activity or by other mechanisms unrelated to
antioxidant effect.
Key ward: Melatonin, Melasma, antioxidant,
INTRODUCTION
Melasma is one of the most common causes of acquired, symmetric hypermelanosis of
the face characterized by irregular light- to gray-brown patches on sun-exposed areas
(Grimes, 1995). The most common sites of involvement are the cheeks, forehead, upper
lip, nose, chin, and occasionally the forearms (Sivayathorn, 1995). Melasma seen mainly
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
in women at any time during the years of reproductive activity, it may be seen in men,
and it tends to occur more often in dark skinned individuals ( Bleehen et al., 1992).
Melasma usually distributed as one of three clinical patterns; centrofacial, malar, and
mandibular ( Sanchez et al., 1981). Melasma can also be divided into three types
according to Wood’s light examination of the skin (Grimes, 1995). The epidermal type
has increased melanin predominantly in the basal and suprabasal epidermis with
accentuation by Wood’s lamp. The dermal type has melanin-laden macrophages in a
perivascular distribution in superficial and deep dermis, with no Wood’s lamp
accentuation. The mixed type has both elements and appears as a deep brown color, with
Wood’s lamp accentuation of only the epidermal component (Pathak, 1986).
Various factors and causes are responsible for the pathogenesis of melasma, but UV
exposure, genetic influences, and hormonal changes are the most commonly cited
etiologic factors (Pathak, 1986). Many therapeutic agents are available but are often
unsatisfactory, including sunscreen and hypopigmenting agents like hydroquinone,
Tretinoin, and Azelaic acid. The most commonly used hypopigmenting agent for the
treatment of melasma is hydroquinone, which reduces the conversion of L-dopa to
melanin by inhibiting the enzyme tyrosinase, hydroquinone used alone or in combination
with other therapies, such as tretinoin, topical corticosteroids, and/or superficial peeling
agents( Balina & Graup, 1991),(Guevara & Pandya, 2001),( Hurly et al., 2002). Recently,
it has been demonstrated that the generation of oxygen free radicals in response of skin
exposure to the sun light is involved in the pathogenesis of melasma. The administration
of antioxidants may decrease the effects of oxidative damage induced by UV radiation on
skin pigmentation (Huh et al., 2003).
Melatonin is a hormone with multiple functions in human, synthesized and secreted by
the pineal gland in response to changes in the darkness and light environment of the
human (Brzezinski,1997). It is a powerful antioxidant and the most potent free radical
scavenger known (Sener et al., 2003). A distinct dose-response relationship was observed
between the topical use of melatonin and the degree of UV-induced damage, melatonin
enhances the ability of the skin to repair itself from free radical-induced damage during
day light hours (Ryoo et al., 2001). Melatonin, vitamin C, and vitamin E, as antioxidants,
may function in melasma by reducing UV-induced free radicals. We chose melatonin not
only due to its powerful antioxidant activity, but also for its effect on the hormones that
involved in the pathogenesis of melasma, like melanocytes stimulating hormone (MSH),
estrogen, and progesterone (Snell & Beschitz, 1960). This study was performed to
evaluate the possible effects of melatonin (alone or in combination with sunscreen) in the
improvement of melasma patients, and comparing these hypopigmentic effects with
those produced by hydroquinone.
MATERIALS AND METHODS
This preliminary clinical study was carried out on 46 subjects, 36 patients with melasma
(22 females and 14 males) aged (17-38) years with a mean of age (26.3 ± 5.2) years, and
have a disease duration of (4.6 ±3.2) years. The patients included in this study were
diagnosed as having epidermal type of melasma, were free from apparent other diseases.
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
The patients were under dermatologist supervision during the period of treatment. All
patients were instructed to quit any other depigmenting and sun-protecting medications at
least two weeks before starting the treatment. The patients were allocated into four
groups and according to the treatment schedule indicated, as follows:
Group A: Include 10 patients (3 males and 7 females) treated with 5% melatonin cream
prepared for this purpose in a two daily doses at afternoon and night.
Group B: Include 10 patients (4 males and 6 females) treated with topical broad-spectrum
sunscreen (SPF 50) in a single morning dose, and with 5% melatonin cream in two daily
doses at afternoon and night.
Group C: Include 10 patients (4 males and 6 females) treated with 5% melatonin cream in
two daily doses at afternoon and night and with 3mg/day melatonin tablet in a single
daily dose at bedtime.
Group D: Include 6 patients (3 males and 3 females) treated with 4% hydroquinone
cream in two daily doses at afternoon and night.
Ten healthy subjects (2 males and 8 females) with the same age range as that of patients
(26.5-35) years with a mean of age (29±3.7) years were selected and served as controls
for comparison. In a double blind technique, all patients were received these treatments
for three months, and then received a placebo formula for one month.
Melasma severity evaluated according to the area involved, color, and homogeneity of
melasma using the Melasma Area and Severity Index (MASI) introduced by KimbroughGreen et al., 1994. In this system the face is divided into four areas and each area
represent a specified percentage of the whole face, as follow:
Forehead = 30%, right malar = 30%, left malar = 30%, and chin = 10%.
The MSAI score was calculated by the following equation:
MASI = 0.3 (DF + HF) AF + 0.3 (DMR + HMR) AMR + 0.3 (DML + HML) AML + 0.1
(DC + HC) AC.
Where D = darkness and H = homogeneity, A = area, F = forehead, MR = right malar,
ML = left malar and C = chin
The values 0.3, 0.3, 0.3 and 0.1 represent forehead, right malar, left malar and chin
percentages of total facial area respectively (14). MASI score was measured before
treatment as base line, and every 15 days for 120 days (four months).
To evaluate the roles of oxidative stress in the etiology and pathogenesis and the roles of
antioxidants in treatment of melasma, fresh blood samples were used for
malondialdehyde (MDA) (as a marker of lipid peroxidation), and glutathione (GSH) (as a
marker of the antioxidant system) measurements in plasma. Blood samples were
collected from patients of groups A, B, C, D, and control group by vein puncture, the first
sample was drawn before treatment (as baseline samples), after 45, and 90 days of the
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
treatment, and then after 30 days of placebo treatment to evaluate the change in the
studied parameters.
The student’s t-test and analysis of variance ANOVA were used to examine the degree of
significance, and P value less than 0.05 was considered significant, and P value less than
0.01 was considered highly significant.
RESULTS
The result of this study revealed that all melasma patients in the four groups that treated
with different treatment regimens demonstrated significant reduction in MASI score in
comparison to baseline after 90 days of the treatment. However, monitoring the follow up
period with placebo treatment (for 30 days) showed that group A patients demonstrated
non-significant reduction in MASI score in comparison to the baseline value (P>0.05),
while group B, C, and D patients demonstrated increased MASI score over that achieved
at day 90 which was still significantly different in comparison to baseline value (P<0.05)
as shown in Fig. 1.
Time (days)
15
30
45
60
75
90
105
120
0
% decrease in MASI score
-5
-10
-15
*
*
**
*
* *
*
*
*
-20
-25
*
*
*
*
gr A
*
*
*
-30
-35
*
*
*
*
gr B
*
*
gr C
gr D
*
*
-40
Fig. 1: Effect of treatment with topical melatonin (group A), topical melatonin-sunscreen
(group B), topical melatonin-oral melatonin (group C) and topical 4% hydroquinone
cream (group D) on MASI score.
 = Significantly different with respect to baseline value, P<0.05.
When the effects of the four strategies of treatments (A, B, C and D) were compared at
the end of treatment period (90 days); patients in groups B, C and D demonstrated
significant reduction in MASI score (31.11%, 28.4% and 37.23% respectively) in
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
comparison to that elicited by treatment with topical melatonin only, group A (13.83%)
(P<0.05) as shown in Fig. 2..
MASI Score
Moreover, no significant difference was noticed in the effect produced by treatment with
topical melatonin-sunscreen (group B) or treatment with topical melatonin-oral melatonin
(group C) on percent reduction in MASI score (P>0.05) as shown in Fig. 2. This figure
also revealed that the effect of 4% hydroquinone cream was significant and potent in
improving MASI score than therapy received by group B and C (P<0.05). In addition,
hydroquinone is shown to be the least one exhibited a relapse phenomenon among all
other therapies.
20
18
16
14
12
10
8
6
4
2
0
Baseline
After 90 days
30 days placebo
a
group A
b
b
group B
group C
c
group D
Figure 2. Effect of treatment with topical melatonin (A), topical melatonin-sunscreen
(group B), topical melatonin-oral melatonin (group C) and topical 4% hydroquinone
cream (group D) on MASI score.
 Data are expressed as mean ± SEM.
 Treatment with placebo starts after ending of 90 days of different treatment
regimens.
 Non-identical superscripts (a, b, c) among different groups are consider
significantly different, P<0.05.

P<0.05 with respect to day 90.
At the end of 90 days treatment, the results demonstrated highly significant reduction in
MDA level in comparison to the baseline level (P<0.01) for group A, B, and C patients.
While group D patients that treated with topical hydroquinone showed no significant
reduction in the level of MDA during 90 days of treatment (P>0.05) as shown Fig. 3.
However, stopping the four treatment regimens and continue treatment with placebo for
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
30 days strongly attenuated the effect produced by these four treatment regimens and less
reduction in MDA was reported in all group which is not significantly different from the
baseline level (P>0.05) as demonstrated in Fig. 3. When the effect of the four treatment
regimens is compared at the end of day 90, significant differences in the level of MDA
were reported in groups B, C and D (23.37%, 28.15% and 5.25% respectively) from that
in group A (14.27%) (P<0.05). Moreover, MDA level in group C is highly reduced but
not significantly different from that in group B as demonstrated in Fig. 4.
Another oxidative stress marker measured is plasma GSH, after 90 days treatment,
significant elevation in the level of GSH is reported when topical melatonin is given
alone (group A), or with sunscreen (group B), or with oral melatonin (group C) in
comparison to baseline level (P<0.05).
Time (days)
45
90
120
% decrease in MDA level
5
0
-5
-10
*
*
-15
*
*
gr A
-20
-25
-30
*
gr B
*
gr C
gr D
Fig 3: Effect of treatment with topical melatonin (group A), topical melatonin-sunscreen
(group B), topical melatonin-oral melatonin (group C) and topical 4% hydroquinone
cream (group D) on the plasma MDA levels. * = Significantly different with respect to
baseline value, P<0.05.
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
Baseline
After 90 days
30 days placebo
MDA level (umol/L)
3
2.5
c
2
a
b
b
group B
group C
1.5
1
0.5
0
Control
group A
group D
Fig. 4. Effect of treatment with topical melatonin (A), topical melatonin-sunscreen (group
B), topical melatonin-oral melatonin (group C) and 4% hydroquinone (group D) on
the plasma MDA levels.
 Data are expressed as mean ± SEM.
 Treatment with placebo starts after ending of 90 days of different treatment
regimens.
 Baseline values in all treatment groups were significantly different from control.
 Non-identical superscripts (a, b, c) among different groups are consider
significantly different, P<0.05.

P<0.05 with respect to day 90.
Moreover, treatment with topical 4% hydroquinone cream (group D) showed not
significant elevation in the level of GSH during 90 days of treatment (P>0.05) as
presented Fig. 5. Again, stopping these four modes of treatment and continuing treatment
with placebo for 30 days strongly abolished the previous effects elicited by these four
regimens with the result of elevation in GSH levels, a value which not significantly
different from the baseline levels (P>0.05) as shown in Fig. 5. When the effect of the four
treatment regimens is compared at the end of day 90, significant difference in the level of
GSH was reported only in group D (4.28%) which in comparison to that in group A
(5.76%), group B (5.22%) and group C (5.38%) (P<0.05) as demonstrated in Fig. 6.
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
gr A
% decrease in GSH level
7
gr B
6
gr C
*
*
*
5
gr D
4
3
2
*
1
0
-1
45
90
120
Time (days)
Fig. 5: Effect of treatment with topical melatonin (group A), topical melatonin-sunscreen
(group B), topical melatonin-oral melatonin (group C) and 4% hydroquinone
(group D) on the plasma GSH levels.
* = Significantly different with respect to baseline value, P<0.05.
Correlation analysis between MASI score with the level of both MDA and GSH revealed
the followings:
In group A, good and highly significant correlation was observed between the decreased
MASI score with the decrease in MDA level (r=0.76, P<0.01) (Fig.7A). However, the
decrease in MASI score correlated moderately but non-significantly with increased GSH
level (r=0.58, P>0.05) (Fig. 7B).
8
GSH level (umol/L)
Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
Baseline
After 90 days
30 days placebo
0.3
0.28
0.26
0.24
0.22
0.2
0.18
0.16
0.14
0.12
0.1
0.08
0.06
0.04
0.02
0
a
Control
group A
a
a
group B
group C
b
group D
Fig. 6. Effect of treatment with topical melatonin (A), topical melatonin-sunscreen (group
B), topical-oral melatonin combination (group C) and 4% hydroquinone (group D)
on the plasma GSH levels.
 Data are expressed as mean ± SEM.
 Treatment with placebo starts after ending of 90 days of different treatment
regimens.
 Baseline values in all treatment groups were significantly different from control.
 Non-identical superscripts (a, b, c) among different groups are consider
significantly different, P<0.05.

P<0.05 with respect to day 90.
In group B, the same profile of correlation is noticed as in group A, in that good and
significant correlation existed between the decrease in MASI score with decreased MDA
level (r=0.73, P<0.05)(Fig.8A). In addition, the decrease in MASI score showed
moderate but not significant correlation with increased GSH level (r=0.49, P>0.1) (Fig.
8B).
In group C, good and highly significant correlation is reported between decreased MASI
score and the decrease in MDA level (r=0.78, P<0.01) (Fig.9A). In addition, the
decreases in MASI score were very weakly and non-significantly correlated with the
increase in GSH level (r=0.25, P>0.1) (Fig.9B).
In group D, non significant correlation is reported between decreased MASI score and the
decrease in MDA level (r=0.64, P>0.1) (Fig.10A). In addition, the decrease in MASI
score correlated well but not significantly with the increase in GSH level (r=0.66, P>0.1)
(Fig.10B).
The present study investigated the effectiveness of using melatonin, a powerful
antioxidant, topically alone and in combination with sunscreen and oral dose of
melatonin in the treatment of melasma patients. The hormone, previously applied to the
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
preparations, effectively inhibited α-MSH darkening activity, and was also able to reverse
alpha-melanocyte stimulating hormone (α-MSH)-induced darkening (Castrucci et al.,
1997). Both cyclic guanosin monophosphate (cGMP) and melatonin blocked the
stimulatory effects of cyclic adenosine triphosphate (cAMP) and α-MSH on melanin
production but they left the levels of tyrosinase activity unaffected.
20
20
18
r = 0.76, P<0.01
16
16
14
14
MASI Score
MASI Score
18
12
10
8
12
10
8
6
6
4
4
2
2
0
0
A0
r = 0.58, P>0.05
0.5
1
1.5
B
2
0
0.05
0.1
0.15
0.2
0.25
GSH (umole/L)
MDA (umole/L)
Fig. 7. A: Correlation between MASI score and MDA level, B: Correlation between MASI
score and GSH level in group A patients.
18
18
16
r = 0.73, P<0.05
14
14
12
12
MASI Score
MASI Score
16
10
8
6
10
8
6
4
A
4
2
2
0
0
0
0.5
1
MDA (umole/L)
1.5
r = 0.49, P>0.1
B
0
2
0.05
0.1
GSH (umole/L)
0.15
0.2
0.25
Fig. 8. A: Correlation between MASI scores and MDA level, B: Correlation between MASI
score and GSH level in group B patients
and MDA level in group B patient.
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
18
18
r = 0.78, P<0.01
14
16
12
14
10
12
MASI Score
MASI Score
16
8
6
4
r = 0.25,P>0.1
10
8
6
4
2
2
0
0
0.5
1
MDA (umole/L)
1.5
0
2
0.16
0.165
0.17
0.175
0.18
GSH (umole/L)
0.185
0.19
0.195
0.2
B
A
Fig. 9 A: Correlation between MASI score and MDA level, B: Correlation between MASI
score and GSH level in group C patient.
16
14
16
r = 0.64, P>0.1
14
r = 0.66,P>0.1
12
10
MASI Score
MASI Score
12
8
6
4
10
8
6
4
2
2
0
1.8
1.9
2
MDA (umole/L)
2.1
0
0.155
2.2
0.16
0.165
GSH (umole/L)
0.17
0.175
0.18
B
A
Fig. 10 A: Correlation between MASI score and MDA level, B: Correlation between
MASI score and GSH level in group D patient.
Discussion
It is suggested that whereas MSH stimulates melanogenesis through a cAMP-dependent
mechanism, their must also be an inhibitory cGMP-dependent mechanism, perhaps
activated by melatonin, which operates at some post-tyrosinase step in the melanin
biosynthetic pathway ( Weatherhead & Logan 1981). But another study showed that
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Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42
melatonin was found to have a small inhibitory effect on tyrosinase activity. Melatonin
appeared to act at least at two stages. Pharmacological concentrations of melatonin
diminished the number of α-MSH receptors to about 75% of the control values without
an apparent effect on receptor affinity, and physiological concentrations of melatonin also
appeared to interfere with the intracellular events coupling increased cAMP levels and
induction of the tyrosinase (Valverde et al., 1995). Cyclic-AMP has been suggested to
transduce the lightening effect of melatonin in frog skin melanophores, and the finding
that MSH-induced cAMP increase is a sufficient signal for pigment dispersion and that
decrease of cAMP induced by melatonin induce aggregation of melanin-containing
granules in perinuclear zone, which result in blanching of the cell (White et al., 1987).
Melatonin is now known to be a multifaceted free radicals scavenger and antioxidant. It
detoxifies a variety of free radicals including superoxide, hydroxyl radical, peroxynitrite
anion, singlet oxygen and nitric oxide (NO). Additionally, it effectively stimulates several
antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase
(GSH-Px), glutathione reductase (GSH-R) that metabolize active oxygen species to
inactive products (Liu & Zheng 2003). When melanocytes synthesize and transfer
melanin to the surrounding keratinocytes. Keratnocytes produce paracrine factors that
affect melanocytes proliferation, dendricity, and melanin synthesis. The keratinocyte
nitric oxide synthase (NOS) is involved in this process, and NO is secreted in response to
UVA and UVB radiation, suggesting an important role of NO in UV-induced
melanogenesis, and this effect is reversed by NO scavengers (Romero-Graillent et al.,
1997). The inhibitory effect of melatonin on NOS may also contribute to its antioxidant
capacity ( Pozo & Guerrero 1994).
Addition of sunscreen to topical melatonin rapidly and significantly resulted in improving
melasma score due possibly to combined action of these two agents in the protection of
skin from UV radiation. It has been shown that irradiation of human keratinocytes or
melanocytes with UV easy stimulates the synthesis and release of α-MSH and
adrenocorticotrophin hormone (ACTH), which induce cAMP formation and increase the
proliferation and melanogenesis of human melanocytes (Moro et al 1998). Sunscreen
might decrease the effect of UV light on melanocytes and decrease the formation of free
radicals induced by UV radiation (Patel & Moy 1992), and this might synergize the
antioxidant activity of melatonin in a possible mechanism involving reduction and
scavenging of UV-induced free radicals.
The great percentage improvement of melasma resulted in the group that treated with
combined topical and oral melatonin is strongly suggested that systemic action be
predominant especially when the effect of topical melatonin only was compared to that of
combined topical-oral regimen. This explanation is supported by the finding that the use
of high doses of melatonin may increase its inhibitory effect on MSH and thus on
melanogenesis (Valverde et al., 1995). This study indicates that melatonin powerfully
reduced MDA level and elevated GSH level when given as topical-oral combination
therapy. Melatonin approved to be restoring the amounts of tissue MDA and GSH back
to about control levels (Ozacmak et al., 2005).
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Treatment with topical hydroquinone cream demonstrated superior improvement in
MASI score over all other treatment regimens. However, hydroquinone remains the most
effective topically applied bleaching agent approved by the FDA. Although there is a
correlations exist between the decreased MASI score and decreased MDA level, and
between the decreased MASI score and increased GSH level, it failed to reach the level
of statistical significance (P>0.1). This clearly demonstrated that hydroquinone improves
MASI score and melasma by antioxidant unrelated mechanism and that only by inhibition
of tyrosinase enzyme.
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‫‪Hamadi S. et al., Journal of Arab Universities for Basic and Applied Sciences, Vol.8, 2009, 30-42‬‬
‫تأثيرات الميالتونين موضعيا ً وعن طريق الفم في معالجة مرضى الكلف‬
‫‪1‬سليم حمادي ‪ 2,‬محمد محمود ‪ 3,‬اشواق الجاف ‪4 ,‬علي عبد الرزاق‬
‫‪1‬كلية الصيدلة والعلوم الطبية‪ -‬جامعة البرا‪ -‬عمان االردن ‪ 2,‬كلية الصيدلة‪-‬الجامعة المستنصرية‪ -‬بغداد‪ -‬العراق ‪,‬‬
‫كلية الصيدلة‪-‬جامعة بغداد‪ -‬بغداد العراق و ‪4‬مستشفى الكرامة التعليمي‪ -‬بغداد‪-‬عراق‬
‫‪3‬‬
‫الملخص‬
‫صممت هذه الدراسة لتقييم التأثيرات الموضعية للميالتونين المحضر على شكل كريم باستعماله‬
‫لوحده أو مع واقي للشمس أو مع الميالتونين عن طريق الفم في معالجة مرضى الكلف بالمقارنة مع‬
‫الهيدروكوينون كعالج قياسي ‪.‬‬
‫أجريت الدراسة السر يريه التمهيدية بالطريقة العمياء المزدوجة على ‪ 36‬مريضا يعانون من الكلف‬
‫و‪ 10‬أشخاص أصحاء للمقارنة‪ ،‬وقد تم اختيار وتشخيص المرضى في العيادة الخارجية لقسم‬
‫األمراض الجلدية في مستشفى الكرامة العام وبإشراف مباشر من قبل اختصاصي الجلدية طيلة فترة‬
‫الدراسة‪ .‬تم تقسيم المرضى إلى أربعة مجاميع‪ ،‬ثم عالج مرضى المجموعة األولى موضعيا"‬
‫بالميالتونين المحضر ومرضى المجموعة الثانية بالميالتونين الموضعي باإلضافة إلى واقي للشمس‬
‫‪ ،‬أما مرضى المجموعة الثالثة فعولجوا موضعيا" بالميالتونين المحضر إضافة إلى الميالتونين عن‬
‫طريق الفم‪ ،‬وتم عالج مرضى المجموعة الرابعة بالهيدروكوينون الموضعي ‪ ،%4‬استمر العالج‬
‫مدة ‪ 90‬يوم تبعتها ‪ 30‬يوم من العالج )‪ (Placebo‬المموه‪ .‬في نهاية فترة العالج ( ‪90‬يوم) أظهرت‬
‫نتائج هذه الدراسة انخفاض ملحوظ في شدة المرض في جميع مرضى الكلف وبنسب متفاوته استنادا‬
‫الى مقياس ‪ MASI‬وكذلك أظهرت النتائج انخفاض في مستوى المالوندايلديهايد‪ ,‬وارتفاع في‬
‫مستوى الكلوتاثايون بعد فترة الدراسة‪ ,‬في كل المجاميع وبمستويات مختلفة‪.‬‬
‫تقترح الدراسة الحالية إن إلعطاء مرضى الكلف مادة الميالتونين موضعيا أو عن طريق الفم تأثير‬
‫ايجابي في العالج عن طريق تأثيره المانع لألكسدة أو عن طريق تأثيرات أخرى مختلفة غير متعلقة‬
‫بتأثيره المانع لألكسدة‪.‬‬
‫‪15‬‬