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Effects of Oral Antioxidants on Lesion Counts Associated with Oxidative Stress and Inflammation in Patients with Papulopustular Acne

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Background: There has been an increasing focus on the extent to which oxidative stress and inflammation are involved in the pathophysiology of acne. The aim of this study is to investigate the effect of oral Silymarin, N-acetylcysteine and Selenium in the treatment of acne vulgaris. Methods: A randomized prospective clinical trial was carried out on 56 patients with acne vulgaris who were examined clinically by dermatologist and classified according to disease severity. Serum levels of Glutathione, Malondialdehyde and Interleukine-8 in the acne patients were measured pre- and eight weeks post-treatment with oral antioxidants and compared to that of 28 healthy volunteers. The clinical follow- up was done every two weeks to assess the changes in the number of inflammatory lesions. Results: Administration of antioxidants to patients with acne vulgaris significantly reduce serum Malondialdehyde level; and increased serum level of Glutathione after eight weeks compared to pre-treatment value, also significantly reduce Interleukine-8 serum levels and the number of inflammatory lesions in patients with acne compared to placebo. Conclusion: The results obtained in this study clearly showed the beneficial effect of Silymarin, N-acetylcysteine and Selenium to patients with acne vulgaris as indicated by the clinical improvement that strongly and positively correlated with improvement in biochemical data.
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Research Article Open Access
Clinical & Experimental
Dermatology Research
Sahib et al., J Clin Exp Dermatol Res 2012, 3:5
http://dx.doi.org/10.4172/2155-9554.1000163
Volume 3 • Issue 5 • 1000163
J Clin Exp Dermatol Res
ISSN:2155-9554 JCEDR, an open access journal
*Corresponding author: Dr. Ahmed Salih Sahib Ph.D., Department of
Pharmacology, Al-Kindy College of Medicine, Baghdad, Iraq, Tel: 00964-7901-
585579; E-mail: ahmadsalih@kmc.uobaghdad.edu.iq
Received September 19, 2012; Accepted October 12, 2012; Published
December 19, 2012
Citation: Sahib AS, Al-Anbari HH, Salih M, Abdullah F (2012) Effects of Oral
Antioxidants on Lesion Counts Associated with Oxidative Stress and Inammation
in Patients with Papulopustular Acne. J Clin Exp Dermatol Res 3:163.
doi:10.4172/2155-9554.1000163
Copyright: © 2012 Sahib AS, et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Abstract
Background: There has been an increasing focus on the extent to which oxidative stress and inammation
are involved in the pathophysiology of acne. The aim of this study is to investigate the effect of oral Silymarin,
N-acetylcysteine and Selenium in the treatment of acne vulgaris.
Methods: A randomized prospective clinical trial was carried out on 56 patients with acne vulgaris who were
examined clinically by dermatologist and classied according to disease severity. Serum levels of Glutathione,
Malondialdehyde and Interleukine-8 in the acne patients were measured pre- and eight weeks post-treatment with oral
antioxidants and compared to that of 28 healthy volunteers. The clinical follow- up was done every two weeks to assess
the changes in the number of inammatory lesions.
Results: Administration of antioxidants to patients with acne vulgaris signicantly reduce serum Malondialdehyde
level; and increased serum level of Glutathione after eight weeks compared to pre-treatment value, also signicantly
reduce Interleukine-8 serum levels and the number of inammatory lesions in patients with acne compared to placebo.
Conclusion: The results obtained in this study clearly showed the benecial effect of Silymarin, N-acetylcysteine
and Selenium to patients with acne vulgaris as indicated by the clinical improvement that strongly and positively
correlated with improvement in biochemical data.
Effects of Oral Antioxidants on Lesion Counts Associated with Oxidative
Stress and Inflammation in Patients with Papulopustular Acne
Ahmed Salih Sahib1*, Haidar Hamid Al-Anbari2, Mohammed Salih3 and Fatima Abdullah4
1Department of Pharmacology, Alkindy College of Medicine, University of Baghdad, Iraq
2Department of Pharmacology, Al-Nahrain College of Medicine, Baghdad, Iraq
3Department of Immunology, Al-Hussein Teaching Hospital, Kerbalaa, Iraq
4Department of Dermatology, Al-Hussein Teaching Hospital, Kerbalaa, Iraq
Keywords: Acne vulgaris; Papulopustular acne; Oxidative stress;
Inammation; Antioxidants; Silymarin; N-acetylcysteine; Selenium
Introduction
Acne vulgaris is an exclusively human disease and unique condition
of human sebaceous follicles of the face, chest and back that begins in the
prepubertal child. Spontaneous regression is common, but in about 5%
of cases acne persists beyond the age of 25 and extends into the fourth
and h decades of life [1]. Histological studies have shown that right
at the start of the formation of a comedone, T-lymphocytes are present
around the pilosebaceous follicle. Subsequently, Propionibacterium
acnes (P. acnes) play a central role in the inammatory phenomenon
associated with acne. e classical mediators in inammation become
involved prostaglandins, leukotrienes, macrophages, and complements
[2]. Current studies show that some membrane fractions of P. acnes
could sometimes act as super antigen causing amplication of the
inammatory reaction by activation notably of keratinocytes and
release of inammatory cytokines (IL-1α, β-Defensin-2, IL-8) through
the activation of Toll-like receptors [3,4].
It has been reported that oxidative stress induced by Reactive
Oxygen Species (ROS) plays a major role in inammation [5].
Excessive generation of ROS by the immune system could result in
inammatory responses; this can also to be induced by skin irritants
[6]. It has been shown that neutrophil-derived reactive oxygen species
are involved in the irritation and destruction of the follicular wall in
acne patients .Although acne vulgaris is the most frequent disease of
the young population, only few studies on antioxidative system in acne
pathophysiology have been performed [7].
Keep in mind the above interrelated events; it is suitable in this
study to use three well known antioxidants that acting by dierent
mechanisms, Silymarin is believed to act in mammalian tissues as a
potent free radical scavenger, as well as plasma membrane stabilizer,
and thus confers protection to the cells during free radical stress
generated by chemical reaction or radiation. is plant can also reduce
the inammatory mediators produced by P. acne in terms of free radical
scavenging and cytokine reducing ability [8]. N-Acetylcystein is acting
as a source of cysteine for the synthesis of the intracellular anti-oxidant
glutathione [9]. Its antioxidant action is believed to originate from its
being a precursor of Glutathione (GSH), provides the cysteine moiety
that is involved in GSH synthesis, so acts as an indirect antioxidant
through this way. It also possesses a direct free radical scavenging
activity against reactive oxygen species [10]. Selenium is an essential
trace element, participates in the antioxidant defends mechanism
as an integral constituent of Glutathione Peroxidase (GSH-Px), the
antioxidative enzyme, acting as a coenzyme. It is not a direct free radical
scavenger; it enhances the conversion of the oxidized Glutathione
(GSSG) into the reduced form (GSH) by GSH-Px enzyme [11].
e Aim of this Study was to investigate the eects of antioxidants
namely; Silymarin, N-Acetylcysteine and Selenium on lesion counts,
Citation: Sahib AS, Al-Anbari HH, Salih M, Abdullah F (2012) Effects of Oral Antioxidants on Lesion Counts Associated with Oxidative Stress and
Inammation in Patients with Papulopustular Acne. J Clin Exp Dermatol Res 3:163. doi:10.4172/2155-9554.1000163
Page 2 of 6
Volume 3 • Issue 5 • 1000163
J Clin Exp Dermatol Res
ISSN:2155-9554 JCEDR, an open access journal
levels of GSH [12], MDA [13] and IL-8 [14] in the acne patients as well
as healthy volunteers were measured.
Assessment of clinical features in acne (Scoring of Acne)
e clinical follow up was done every two weeks to assess the
changes in the number of inammatory lesions (the papules and the
pustules) and to check any side eects that might appears systemically
or topically. ere are two commonly used measures which are
grading and lesion counting [15]. In 2008, Hayashi N. et al, used lesion
counting to classify acne into four groups. ey classied acne based on
the number of inammatory eruptions on half of the face as 0-5: mild;
6-20: moderate; 21-50: severe; and more than 50: very severe. Since the
present study is dealing with patients with papulopustular type of acne,
the Hayashi scoring in assessing the severity and the progress of the
disease in the acne patients was followed [16]. Patients were educated
neither to squeeze the lesions, nor dig them, as this can aggravates
the lesions. ey were also told to clean their faces several times daily
using the medicated cleansers to get rid of the accumulated sebum.
e number of the inammatory lesions was registered every visit
every two weeks for each patient till the end of the eight weeks, and the
percentages of changes in the lesions were analyzed statistically. e
percent reduction in lesion count was calculated through the following
equation:
[Baseline lesion counts-(x) week’s lesion counts]/Baseline lesion
counts×100%
Assessment of side eects
Side eects would be looked for by asking the patients each visit
about any abnormal eect that appeared throughout the whole course
of treatment.
Statistics
Results represented as the mean ± standard deviation, using
Statistical Package for Social Science SPSS version 18.0 under Windows
seven, Microso Excel 2010. Student t-test and One-way Analysis of
Variance (ANOVA) test would be used to compare between the
dierent groups concerning pre- and post- treatment values. P ≤ 0.05
considered signicant change, and P ≤ 0.01considered high signicant
change. Pearson’s correlation and regression test would be used to
compare between the clinical ndings and the laboratory ndings.
Results
Data in table 1 showed that there was non-signicant dierence
between the baseline values of serum levels of GSH, MDA, and IL-8
for patients who were treated with Silymarin, N-Acetylcysteine and
Selenium and the patients who were treated with placebo, in contrast,
comparison with healthy subjects revealed highly signicant change P
0.01 in the baseline level of mentioned markers. On the contrary,
oxidative status and inammation in patients with acne vulgaris; and
to nd out any possible correlation between oxidative stress markers
Glutathione (GSH) and Malondialdehyde (MDA) as well as the
inammatory marker Interleukine -8 (IL-8) with the clinical features
of acne.
Materials and Methods
A randomized, single-blind, prospective, placebo controlled trial
which was carried out at the dermatologic outpatient clinic in Al-
Hussein teaching hospital, Karbalaa health directorate-Iraq, during
the period between December 2011 and May 2012. Fiy-six patients of
both sexes, their age ranges from 14-30 years old have been enrolled in
this study, divided into four groups, each include 14 patients. Complete
history was taken from each patient about age, gender, marital state;
duration of the disease, previous treatment and past medical history.
e Inclusion Criteria were: Clinical examination was done by the
dermatologist, the selected patients were complaining of papulopustular
acne, and had never taken previous acne therapy treatment, or stopped
any systemic and topical treatment at least one month before starting
the present study therapies. While Exclusion Criteria include: Patients
with chronic diseases, diabetic patients, those who were taking
steroids, hypercholestremic patients, and patients with hepatic and/
or renal insuciency were excluded from the study. Pregnant and
lactating women were also excluded from the study, as well as, patient
with known hypersensitivity to any of the drugs that were used in the
study. e duration required for each individual patient to complete
the course of the treatment was eight weeks, clinical and laboratory
assessment would be carried out at baseline, during and by the end of
this period. In addition to that, 28 age and sex matched healthy people
(16 males and 12 females), were tested for their serum levels of GSH,
MDA and IL-8 to compare these results with those of the patients with
acne at the starting point of the study. Each volunteer was told about
the study, and an oral consent was obtained from each one.
Groups of patients
e study was performed with 56 patients randomly allocated into
four groups as follow:
Group (1): includes 14 patients , eight males and six females, were
treated with silymarin 210 mg/day orally : one tablet of Silymarin 70
miligram (LEGALON ; Madous company) three times daily aer meals
and a topical moisturizing cream once daily at bed time (Aqua Rosa
cream).
Group (2): includes 14 patients, seven males and seven females:
were treated with N-acetylcysteine 1200 mg/day orally: one eervescent
tablet of N-acetylcysteine 600 milligram (FLUIMUCIL; Zambon
company) twice daily and the same topical moisturizing cream once
daily at bed time.
Group (3): includes 14 patients, eight males and six females were
treated with Selenium 200 mcg/day orally: one tablet of Selenium 100
microgram (SELENIUM; Jamieson company) twice daily and the same
topical moisturizing cream once daily at bed time.
Group (4): includes 14 patients, seven males and seven females:
were treated with placebo capsule (500 milligrams of glucose powder)
once daily orally and the same topical moisturizing cream once daily
at bed time.
Blood samples were collected from the patients as well as the
healthy volunteers. At the starting point of the study the baseline serum
Parameters Healthy (n=28) Patients (n=56)
S. GSH (µg / ml) 1.61 ± 0.99 0.65 ± 0.22**
S. MDA (µg / ml) 5.46 ± 2.82 8.68 ± 1.55**
S. IL-8 (pg / ml) 36.65 ± 25.73 61.17 ± 39.92*
Results represent mean ± Standard deviation
**represents highly signicant P ≤ 0.01 change between healthy subjects and
patients
*represents signicant P ≤ 0.05 change between healthy subjects and patients
Table 1: Baseline values of serum glutathione, malondialdehyde and interleukine-8
for patients with acne compared to healthy subjects.
Citation: Sahib AS, Al-Anbari HH, Salih M, Abdullah F (2012) Effects of Oral Antioxidants on Lesion Counts Associated with Oxidative Stress and
Inammation in Patients with Papulopustular Acne. J Clin Exp Dermatol Res 3:163. doi:10.4172/2155-9554.1000163
Page 3 of 6
Volume 3 • Issue 5 • 1000163
J Clin Exp Dermatol Res
ISSN:2155-9554 JCEDR, an open access journal
there was a highly signicant dierence in the last (aer eight weeks of
treatment) values of serum level of GSH and MDA, and only signicant
dierence in the level of IL-8 between the patients who were treated
with dierent antioxidants and the patients who were treated with
placebo (Table 2).
Results showed that silymarin caused an elevation in serum GSH
level by about three folds (271%), and decreased MDA and IL-8 by
39.2% and 80% respectively in acne patients aer eight weeks period of
use (Table 2). Concerning the eect of silymarin on the clinical feature
(score), the number of inammatory lesions was reduced every two
weeks during the use of silymarin, the reduction was signicant (when
compared to the baseline) at the sixth and the eighth week (P value
≤ 0.05). Aer eight weeks of treatment, the reduction in lesion count
was 53%, this reduction was statistically signicant P ≤ 0.05. While non
signicant reduction in number of inammatory lesions happened
with placebo (Table 3). On the other hand, N-Acetylcysteine caused an
elevation in serum GSH by two folds (205%), and decreased MDA and
IL-8 by 38.8% and 72% respectively aer using for eight weeks, (Table
2). Clinically, there was non-signicant dierence between the baseline
number of inammatory lesions between the patients who were treated
with N-Acetylcysteine and the patients who were treated with placebo.
e number of inammatory lesion was reduced every two weeks
by using N-Acetylcysteine, and the reduction was signicant (when
compared to the baseline) at the sixth and the eighth week (P value
0.05). Aer eight weeks of treatment, the percentage of reduction in
the total count of inammatory lesions was 50%, which was statistically
signicant. No signicant reduction in number of inammatory lesions
happened with placebo (Table 3). In case of selenium, an elevation in
serum GSH by two folds (201%), and decreased MDA and IL-8 by 35%
and 71% respectively aer using for eight week, (Table 2). Furthermore,
there was non-signicant dierence between the baseline number
of inammatory lesions between the patients who were treated with
Selenium and the patients who were treated with placebo. Although
there was a reduction in the number of inammatory lesions by using
Selenium in each visit (every two weeks) compared to placebo, but this
reduction was not signicant compared to the baseline (Table 3).
Correlation of the inammatory lesion number (clinical
score) with the serum level of GSH, MDA and IL-8 (laboratory
parameters)
Using Pearson’s correlation, results showed that base line value
of serum GSH negatively correlated with number of inammatory
lesions, r=-0.753, P 0.001 (Figure 1). Another correlation was done
between GSH (post-treatment with antioxidants) and inammatory
lesions number aer eight weeks, signicant negative correlation was
produced P ≤ 0.05, r=-0.334; (Figure 2). Concerning the correlation of
the inammatory lesion number with serum MDA, highly signicant
positive correlation was found between MDA baseline value and
inammatory lesions number, P 0.001, r=0.749 (Figure 3). Besides
that, aer eight weeks use of dierent antioxidants, there was also highly
signicant positive correlation between MDA value and inammatory
lesions number P ≤ 0.001, r=0.481(Figure 4).
On the other hand, highly signicant positive correlation was
found between IL-8 (pre-treatment) and inammatory lesions number
at the baseline, P ≤ 0.001, r=0.811 (Figure 5); as well as, correlation was
done between IL-8 and inammatory lesions number aer 8 weeks, a
highly signicant positive correlation was present P 0.001, r=0.828
(Figure 6).
Discussion
ere has been an increasing focus on the extent to which oxidative
stress is involved in the pathophysiology of acne; studies have shown
that patients with acne are under increased cutaneous and systemic
oxidative stress [17]. Additional researches seem to conrm that
lipid peroxidation is the driving force behind the progression of
comedogenesis and inammation in acne, the marked increase in
lipid peroxidation once inammation is ongoing is to be expected.
Undoubtedly Reactive Oxygen Species (ROS) can provoke the secretion
of inammatory cytokines; however, once initiated, inammatory
chemicals cause a subsequent increase in ROS production [18]. Based
on this theory, the present study was carried out to check the eects
of Silymarin, N-Acetylcysteine and Selenium in patients with acne.
Results in the present study revealed that there is a highly signicant
(P ≤ 0.01) decrease in serum levels of GSH, highly signicant increase
Results represent mean ± Standard deviation
**represents highly signicant P ≤ 0.01 change between treatment groups and placebo
*represents signicant P ≤ 0.05 change between treatment groups and placebo
Table 2: Effects of Silymarin, N-Acetylcysteine and Selenium on serum glutathione, malondialdehyde and interleukine-8 for patients with acne compared to placebo after
eight weeks.
Variables Timing G1 Silymarin G2 N-Acetylcysteine G3 Selenium G4 placebo
S. GSH (µg/ml ) Pre 0.593 ± 0.17 0.719 ± 0.24 0.73 ± 0.15 0.57 ± 0.25
Post 1.604 ± 0.75** 1.48 ± 0.67** 1.47 ± 0.58** 0.56 ± 0.28
S. MDA (µg/ml ) Pre 8.94 ± 0.99 8.26±1.23 8.01 ± 1.1 9.53 ± 2.21
Post 5.44 ± 1.79** 5.05 ± 1.74** 5.2 ± 1.95** 9.64 ± 2.2
S. IL-8 (pg/ml ) Pre 66.38 ± 40.35 68.53 ± 37.93 58.29 ± 46.9 51.45 ± 35.71
Post 13.2 ± 13.2*18.93 ± 15.13* 17 ± 11.49* 55.32 ± 41.23
Results represent mean ± Standard deviation
*Represents signicant change P≤0.05 between treatment groups vs. placebo
Table 3: Effects of Silymarin, N-Acetylcysteine and Selenium on the number of inammatory lesions on half - face of patients with acne compared to placebo after eight
weeks.
Variables Base line 2weeks 4weeks 6weeks 8weeks
G1/Silymarin 19.57+7.68 16.93+6.7 14.21+5.85 11.64+5.42*9.14+4.75*
G2/N-Acetylcysteine 19.07+6.6 16.71+5.65 14.0+4.88 11.64+4.05*9.5+3.59*
G3/Selenium 18.86+8.12 17.14+7.66 15.0+7.26 13.43+6.89 11.93+6.83
G4/placebo 19.28 ± 9.29 18.71 ± 9.381 18 ± 8.72 17.64 ± 8.67 17.14 ± 8.77
Citation: Sahib AS, Al-Anbari HH, Salih M, Abdullah F (2012) Effects of Oral Antioxidants on Lesion Counts Associated with Oxidative Stress and
Inammation in Patients with Papulopustular Acne. J Clin Exp Dermatol Res 3:163. doi:10.4172/2155-9554.1000163
Page 4 of 6
Volume 3 • Issue 5 • 1000163
J Clin Exp Dermatol Res
ISSN:2155-9554 JCEDR, an open access journal
in serum levels of MDA and a signicant increase in serum levels of
IL-8 were found in acne patients compared to healthy people at the
baseline. Results clearly demonstrated the existence of oxidative stress
and inammation in acne patients.
Administration of silymarin caused an elevation in serum GSH
by about three folds (271%), and decreased MDA and IL-8 by 39.2%
and 80% respectively in acne patients, and a reduction in lesion count
(percentage) by 53% aer eight weeks period of use, this reduction
was statistically signicant. Silymarin acts by many mechanisms that
may include antioxidative, anti lipid peroxidative, anticarcinogenic,
antibrotic, anti-inammatory, membrane stabilizing, immune-
modulator and liver regenerating mechanisms [19,20]. e anti-
inammatory eects of silymarin are based on multiple activities
including mast cell stabilization, inhibition of neutrophil migration,
Kuppfer cell function inhibition and inhibition of leukotriene and
prostaglandin formation [21]. e avounoids of Silibum marianum
may also exert their anti-inammatory action through inhibition of
lipooxygenase and cyclooxygenase-2 activity [22]. Leukotriene B4
(LTB4) induces recruitment and activation of neutrophils, monocytes
and eosinophils, it also stimulates the production of several pro-
inammatory cytokines and mediators that augment and prolong
tissue inammation [23]. Leukotrienes B4, leukotriene C4 are shown
to have a mitogenic eect on keratinocytes and may therefore takes
part in mediating hyperproliferation in the pilosebaceous unit [24]. A
study done by Zouboulis (2009) found that 5-lipoxygenase inhibitor
(Zileuton) is eective in treatment of acne vulgaris [25]. e molecular
bases of the anti-inammatory eects of silymarin might be related
to inhibition of the transcription factor NF-κB, which regulates
-10
0
10
20
30
40
0 0.5 1 1.5 2
Inammatory lesion no.
GSH (mcg/ml)
Figure 1: Correlation between serum GSH pretreatment and inammatory
lesion no. (baseline) in all patients group, r=-0.753.
0
5
10
15
20
25
30
35
0 0.5 1 1.5 2 2.5 3 3.5
Inflammatory lesion no.
GSH (mcg/ml)
Figure 2: Correlation between serum GSH post-treatment and inammatory
lesion no. (8wk) in all patients group, r= - 0.334.
0
5
10
15
20
25
30
35
40
0 2 4 6 8 10 12 14
Inammatory lesion no.
MDA (mcg/ml)
Figure 3: Correlation between serum MDA pre-treatment and inammatory
lesion no. (baseline) in all patients group, r = 0.749.
0
5
10
15
20
25
30
35
0 2 4 6 8 10 12 14 16
Inammatory lesion no.
MDA (mcg/ml)
Figure 4: Correlation between serum MDA post-treatment and inammatory
lesion no. (8wk) in all patients group, r = 0.481.
0
5
10
15
20
25
30
35
40
0 50 100 150 200
Inammatory lesion no.
IL-8 (pgl/ml)
Figure 5: Correlation between serum IL-8 pretreatment and inammatory lesion
no. (baseline) in all patients group, r = 0.811.
0
5
10
15
20
25
30
35
0 20 40 60 80 100 120 140
Inammatory lesion no.
IL-8 (pgl/ml)
Figure 6: Correlation between serum IL-8 posttreatment and inammatory
lesion no. (8wk) in all patients group, r = 0.828.
Citation: Sahib AS, Al-Anbari HH, Salih M, Abdullah F (2012) Effects of Oral Antioxidants on Lesion Counts Associated with Oxidative Stress and
Inammation in Patients with Papulopustular Acne. J Clin Exp Dermatol Res 3:163. doi:10.4172/2155-9554.1000163
Page 5 of 6
Volume 3 • Issue 5 • 1000163
J Clin Exp Dermatol Res
ISSN:2155-9554 JCEDR, an open access journal
and coordinates the expression of various genes involved in the
inammatory process [26].
Over all, the powerful antioxidant, anti-inammatory eect of
silymarin has been clearly shown above, which may represent rational
explanation for the results obtained in this study when silymarin was
used for eight weeks, and was very eective to treat acne patients.
Administration of N-Acetylcysteine caused an elevation in serum GSH
by two folds (205%), and decreased MDA and IL-8 by 38.8% and 72%
respectively aer using for eight weeks, and caused a reduction in the
total count of inammatory lesions, the percentage of reduction was
50%, which was statistically signicant. N-Acetylcysteine (NAC), has
been studied and utilized as a source of cysteine, which is a precursor
in the synthesis of reduced Glutathione (GSH) and as a direct free
radical scavenger that protects cells from oxidant damage [27]. It has
also been suggested that the drug has anti-inammatory properties by
suppressing the activation of nuclear factor kappa (NF-kB) [28,29] . In
addition, it was found that NAC inhibited the production of TNF-α,
IL-6 and IL-8 in GSH-depleted human in vitro [30]. All these eects
strongly support the results obtained in the present study, where NAC,
administered in a dose of 1200 mg daily for a period of eight weeks was
really eective in treating patients with acne.
Administration of Selenium to acne patients result in elevation in
serum GSH by two folds (201%), and decreased MDA and IL-8 by 35%
and 71% respectively aer using for eight weeks. It reduced the number
of inammatory lesions, yet; this reduction was statistically non
signicant. e essential trace element, selenium, acts as an integral
constituent of the antioxidative enzyme Glutathione Peroxidase (GSH-
Px), which detoxies Hydrogen Peroxide (H2O2) and organic lipid
peroxides at the expense of reduced Glutathione (GSH). e selenium-
dependent enzyme glutathione peroxidase (GSH-Px) recycles
glutathione, reducing lipid peroxidation by catalyzing the reduction
of peroxides, including hydrogen peroxide; this represents a crucial
component of antioxidative potential in humans [31]. Several in vivo
studies have shown that serum selenium levels are inversely correlated
with serum concentrations of IL-8 [32]. A study has reported the
molecular basis of the anti-inammatory property of selenium to be
driven by modulation of 15deoxy-Prostaglandin J2 metabolism [33].
Accordingly, the ability of selenium to increase GSH and decrease
MDA and IL-8 in addition to its eectiveness to reduce the lesion
number aer eight weeks of using selenium as a proposed acne therapy
may be explained.
e use of the well known antioxidants (Silymarin, N-Acetylcysteine
and Selenium) orally, resulted in elevating the serum level of GSH
signicantly and reducing the serum level of MDA and IL-8 and in
the acne patients. Furthermore; all the three antioxidants reduced
the number of the inammatory lesions, although the percentage
and the level of signicance of this reduction was not the same for all
the agents. e results of the present study are compatible with other
studies regarding the presence (and targeting) of oxidative stress and
inammation in acne. In 2011, a study done by Khurana et al, 100
patients with untreated mild to moderate acne vulgaris were included.
eir measurement results showed that Lipid peroxidation (MDA) was
signicantly increased in those patients implying signicant oxidative
membrane damage, while antioxidative capacity measured in terms
total thiol was signicantly low [34]. Arican et al. studied the role of
oxidative stress in 43 acne patients, they found that Catalse and G6PD
levels in patients were statistically decreased, and MDA levels were
found to be statistically increased [35]. Rubin et al. discovered that the
self-administration of an omega-3 sh oil-based nutrient combination
for two months have some inuence on the acne process, and perhaps
more importantly, on mental outlook. e average inammatory lesion
count at baseline was 20.8 which decreased to 6.8 aer two months [36].
On the other hand, results of this study showed that correlation between
the number of inammatory lesions and serum levels of GSH, MDA
and IL-8 pre- and post-treatment revealed that there was signicant
negative correlation between the number of inammatory lesions
and the serum levels of GSH, at the same time, there was signicant
positive correlation between the number of inammatory lesions
and the serum levels of MDA, beside signicant positive correlation
between the number of inammatory lesions and the serum levels of
IL-8. erefore, targeting these changes, through using agents that can
increase GSH level, decrease MDA and IL-8 serum levels represent a
good therapeutic option for treating inammatory acne.
Depending on the results obtained by this study, it can be
concluded that oxidative stress and inammation exist in patients with
acne vulgaris and may be considered as contributing factors involved
in the aetiopathogenesis of the disease. Administration of Silymarin,
N-Acetylcysteine and Selenium resulted in signicant correction of the
disturbed antioxidative status of acne patients, and a marked reduction
in the inammation, in addition to clinical improvement represented
by reduction in the number of inammatory lesions in patients with
papulopustular acne. Glutathione is negatively correlated, while
malondialdehyde and interleukin-8 are positively correlated with
the clinical features (score) of acne, therefore targeting these changes
with oral antioxidants might represent a new therapeutic strategy in
treatment of acne vulgaris.
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... While N-acetylcysteine helps improve inflammatory lesions of acne by quenching reactive oxygen species, inhibition of leukotrienes and prostaglandins, stabilization of membranes and inhibiting lipid peroxidation, 90 its effect on comedones has been described as very poor, which can be due to reduced sebum or inhibition of oval Pityrosporum (a potential comedogenic organism that has been detected in comedones). 91 A single-blind randomized study conducted in Iraq showed a significant reduction in the number of inflammatory lesions in 14 patients treated with 1200 mg of NAC compared to the placebo group. ...
... 91 A single-blind randomized study conducted in Iraq showed a significant reduction in the number of inflammatory lesions in 14 patients treated with 1200 mg of NAC compared to the placebo group. 90 Another double-blind study showed a significant reduction in the number of comedones in a group of 65 patients receiving NAC 5% gel over 8 weeks compared to the control group (34 patients). 91 ...
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Acne Vulgaris is one of the most common dermatologic disorders affects people of all races and ethnicities and has many adverse effects on the quality of life. The increased bacterial resistance to antibiotics has reduced the effectiveness of treatment with these agents. There is an increasing focus on the involvement of oxidative stress in the pathophysiology of acne. This study investigates the effect of N‐acetylcysteine as an antioxidant in the treatment of acne vulgaris. This systematic review was conducted through a search in databases such as Science Direct, PubMed, Scielo and Medline using keywords including acne vulgaris, anti and N‐acetylcysteine, and all the keywords associated with each of the subtitles. The factors affecting the occurrence and expansion of acne include increased sebum synthesis, hyperkeratinization of pilosebaceous units, colonization with Propionibacterium acnes, and increased release of inflammatory mediators and ROS. Studies have shown that glutathione stimulation following the administration of NAC increases glutathione levels for the detoxification of oxygen free radicals. Moreover, NAC prevents the synthesis and release of inflammatory cytokines such as TNF‐α, IL‐8, IL‐6, MP9, and IL‐1β and has shown antibacterial activities against important bacteria including E.coli, S. epidermidis, Pseudomonas and Klebsiella. This medication has anti‐proliferative effects and is also used for excoriation and PCOD. The results of the present study showed the beneficial effects of using N‐acetylcysteine in patients with acne vulgaris in terms of the disease complications and comorbidities. Given its diverse functional mechanisms, this medication can be used to treat acne and its consequences. This article is protected by copyright. All rights reserved.
... ROS plays a major role in inflammation inducing inflammatory mediators' productions such as prostaglandins, leukotrienes, chemokines, cytokines (TNFα, IL1β, IL6) and NF-κB activation [6]. Prostaglandins and leukotrienes are synthesized respectively through cyclooxygenases (COX) and lipoxygenase (LOX) activation. ...
... 1.25 mL of potassium hexacyanoferrate solution [K 3 Fe (CN)6 ] (1% in water). After 30 min incubation at 50 °C in a water bath, 1.25 mL of trichloroacetic acid (10%) was added and the mixture was centrifuged at 2000 rpm for 10 min. ...
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Aims: To determine the phytochemical composition and evaluate the antioxidant and anti-inflammatory properties of methanolic and aqueous extracts from Ampelocissus africana (Lour) Merr rhizomes. Study Design: Phytochemical content and screening, in vitro antioxidant and anti-inflammatory assays. Place and Duration of Study: Department of Traditional Pharmacopoeia and Pharmacy (MEPHATRA / PH) of the Institute for Research in Health Sciences (IRSS) and Laboratory of Applied Biochemistry and Chemistry (LABIOCA), University Joseph KI-ZERBO in Ouagadougou between April and August 2020. Methodology: The antioxidant activity of both extracts of the plant was assessed using DPPH radical scavenging, ABTS+ radical cation decolorization, ferric ion reduction and lipid peroxidation inhibition in rat liver assays. The anti-inflammatory activities in vitro were measured on the ability of the extract to inhibit the activity of enzymes such as 15-lipoxygenase, phospholipase A2 (PLA2) and cyclooxygenases (COX-1 and COX-2). Results: This study revealed that the total phenolic contents of the extracts varied from 471.79 ± 1.71 mg GAE/g to 173.88 ± 1.71 mg GAE/g for methanolic and aqueous extract respectively. The extracts were also rich in flavonoids and tannins. The methanolic extract possessed better antioxidant activity with an IC50 of 2.32 ± 0.18 µg/ml for the ABTS, 1.71 ± 0.05 µg/mL for the DPPH, a reducing power agent of 87.44 ± 0.5 mmol AAE /100 g and a percentage inhibition of lipid peroxidation of 52.21%. The methanolic and aqueous extract of A. africana has an inhibitory action on activity of lipoxygenase with IC50 values of 26.09 ± 1.83 μg/mL to 34.32 ± 1.60 μg/mL, respectively. The methanolic extract caused COX-1 inhibition of 36.07%, COX-2 inhibition of 38.31% and PLA2 inhibition of 26.9%. Conclusion: These results showed that the methanolic and aqueous extract from the rhizomes of Ampelocissus africana possessed antioxidant power, inhibitor effect against proinflammatory enzymes.
... While n-acetylcysteine helps improve inflammatory lesions of acne by quenching reactive oxygen species, inhibition of leukotrienes and prostaglandins, stabilization of membranes and inhibiting lipid peroxidation, 71 its effect on comedones is less well defined and could be due to decreased sebum production or inhibition of Pityrosporum ovale, a potential comedogenic organism that has been demonstrated in comedones. 72 A randomized, single-blind trial from Iraq showed that the number of inflammatory lesions decreased significantly in 14 patients who received 1200 mg/day of n-acetylcysteine compared to placebo. ...
... 72 A randomized, single-blind trial from Iraq showed that the number of inflammatory lesions decreased significantly in 14 patients who received 1200 mg/day of n-acetylcysteine compared to placebo. 71 Another double-blind, placebo-controlled trial found that the test group comprising 65 patients who received 5% n-acetylcysteine gel for 8 weeks had significantly reduced the number of comedones compared to patients in the control group (34 patients) who received only placebo. 72 ...
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N-acetylcysteine is a mucolytic drug which is commonly used as an antidote for acetaminophen toxicity. It is a thiol compound, which acts as a donor of cysteine, leading to replenishment of glutathione and thus acts as an antioxidant. It also has anti-inflammatory effects, alters the levels of neurotransmitters, inhibits proliferation of fibroblasts and keratinocytes and causes vasodilatation. Due to these actions, n-acetylcysteine has found use in several dermatologic conditions in systemic and topical form. The drug has been used as an adjuvant in the management of conditions such as toxic epidermal necrolysis, drug hypersensitivity syndrome, trichotillomania, skin picking disorders and onychotillomania, ichthyoses, contact dermatitis, atopic dermatitis, melasma, pseudoporphyria, connective tissue diseases, wound healing and alopecia. It also has a role in protection from radiation-induced skin damage including photo-ageing, photocarcinogenesis and radiation dermatitis. Most indications in dermatology are supported by case reports, small case series and small trials. Higher quality of evidence is needed for its wider use. The drug is cheap and is generally safe with few adverse effects. Thus a greater role is possible for use of n-acetylcysteine in various skin conditions. This review explores the various uses of n-acetylcysteine in the field of dermatology, the evidence supporting the same, the possible mechanisms of action and the adverse effects of the drug.
... Oral 1.200 mg/ gün NAC kullanımıyla inflamatuar lezyon sayısının önemli ölçüde azaldığı gösterilmiştir. 65 Montes ve ark.nın 99 akne hastasında yaptığı bir çalışmada, %5 NAC topikal jel kullanılmasıyla komedon sayılarında belirgin azalma sağlandığı gösterilmiştir. 66 Biyofilm Oluşumu üzerine Etkisi Araştırmalar, NAC'nin, gram-pozitif ve gram-negatif bakteri biyofilmlerine karşı potansiyel antimikrobiyal etkilerini göstermiştir. ...
... This can cause pain, a rise in denaturation of protein, permeability of the vascular tissues and alteration of the membrane [11]. Reactive oxygen species functions greatly in inflammation activating production of inflammatory mediators like the leukotrienes, prostaglandins, cytokines (TNFα, IL1β, IL6), chemokines and activation of NF-κB [12]. Leukotrienes and prostaglandins are synthesized through the pro-inflammatory enzymes; lipoxygenase (LOX) and cyclooxygenases (COX) activation respectively. ...
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... The implication of oxidative stress in the development of acne vulgaris underlines the role of antioxidants in disease management. Sahib et al. [20] stated that the administration of oral antioxidants in the form Silymarin, Selenium and N-acetylcysteine decreased the severity of acne lesions and improved the oxidative status of patients as indicated by serum oxidative stress biomarkers. ...
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Aim. T he paper studies the dynamics of the indicators defi ning the antioxidant system (AOS) and endogenous intoxication in patients with microbial eczema (ME) prior to and following treatment. Materials and methods. The experimental group consisted of patients with ME ( n =30) and the control group comprising somatically healthy individuals ( n =30). In this study, we determined the components of the antioxidant defence system in blood plasma and erythrocyte suspension, as well as assessed endogenous intoxication. Results. The study revealed an imbalance of indicators refl ecting the severity of oxidative stress and endogenous intoxication in patients suffering from ME. Prior to receiving treatment, the experimental group, as compared to the control group, exhibited an increase in catalase activity (CAT) up to 35.93 [32.50; 38.22] mmol / (min • l) ( p < 0.001) and glutathione peroxidase (GPx) up to 1194.27 [1069.50; 1375.78] μmol / (min • l) ( p < 0.001). In addition, there was a decrease in the activity of superoxide dismutase (SOD) to 13.28 [11.35; 14.10] u/l ( p < 0.001), glutathione reductase (GR) to 501.46 [479.77; 542.52] mmol / (min • l) ( p < 0.001) and the concentration of reduced glutathione to 1.64 [1.59; 1.78] μmol / ml ( p = 0.043). We observed no statistically signifi cant changes in the total antioxidant activity (TAA) of blood plasma (0.59 [0.55;0.62] mg/l; р = 0.375) and the sulphhydryl groups (0.44 [0.41;0.47] ODU; р =0.111). The patients with ME exhibited the syndrome of endogenous intoxication (SEI), accompanied by an increase in the content of medium and low molecular weight molecules in plasma to 12.19 [11.20; 13.37] arb. u. ( p < 0.001), with their content in erythrocytes being relatively normal – 15.23 [14.26; 16.44] arb. u. ( p = 0.005). Following the treatment, changes in the studied parameters were of a multidirectional character in relation to the control values. An increased level of CAT and GPx ( р <0,001), as well as lower values of SOD and GR, continued to be observed ( р < 0.001). The TAA in serum ( p = 0.308), sulphhydryl groups ( p = 0.111) and reduced glutathione ( p = 0.107) did not differ signifi cantly from the control values. The treatment did not reverse the SEI: the content of medium and low molecular weight molecules continued to increase in both plasma and erythrocytes, as compared to the control values ( p < 0.001 in both cases). Conclusion. The obtained data confi rm the failure of mechanisms underlying antioxidant defence in patients with ME. Despite the attempt of its compensation by increasing the catalase activity, SOD control values were still not reached. An increase in the GPx activity along with a decrease in GR was observed, which could have lead, in turn, to a decrease in the concentration of reduced glutathione. The failure of the antioxidant defence mechanisms is also indicated by an increase in the content of medium and low molecular weight molecules, as well as by the development of the SEI, resulting from the excessive formation of reactive oxygen species and the inability of the antioxidant system to neutralise them.
... P. acnes produces chemotactic factors for neutrophils which generate a release of inflammatory factors like lysozyme enzymes leading to the destruction of the follicular wall as a result of the phagocytosis. In the inflammatory tissue, reactive oxygen species alter DNA and/or membrane lipids causing cell damage at the inflammation site [3,7,26,27,28]. Based on these observations, the four vegetal extracts incorporated in the cosmetic cream act synergistically in reducing inflammatory reaction mediated by oxidative stress in addition to their antimicrobial activity. Moreover, the other ingredients of the cosmetic cream were chosen for the most suitable properties in acne patients. ...
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H. Schulz Aknepatienten mit entzündlichen Papeln und Pusteln profitieren von der Einnahme antioxidativer Substanzen wie Silymarin, NAcetylcystein oder Selen. In einer randomisierten, prospektiven Studie mit 56 Aknepatienten sank nach achtwöchiger Behandlung nicht nur die Zahl der entzündlichen Hautläsionen, auch biochemische Parameter, die als Maß für den oxidativen Stress gelten, verbesserten sich: Nach achtwöchiger Einnahme war einerseits weniger Interleukin8 und Malondialdehyd im Serum nachweisbar, andererseits mehr von dem Antioxidans Glutathion.
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Tissue inflammation is a major component of the acne process. Leukotriene B(4) (LTB(4)) is considered to be a major player in the development of tissue inflammation. Synthesis of LTB(4) is controlled by the enzyme 5-lipoxygenase. Since Zileuton blocks the activity of 5-lipoxygenase, experimental and clinical studies have been conducted to test mode of function, as well as efficacy and safety of this compound in the treatment of acne vulgaris. Human SZ95 sebocytes and inflammatory cells in vitro express the enzymes of the leukotriene pathway at mRNA and protein levels and enzymes involved in the biosynthesis of LTB(4) are activated in sebaceous glands of acne lesions. Pre-treatment of SZ95 sebocytes with Zileuton partially prevented short-term arachidonic acid-induced effects, such as induction of LTB(4), increase of neutral lipid content and stimulation of interlekin-6 release. Long-term treatment with Zileuton directly reduced the content of neutral lipids and interleukin-6 release from SZ95 seb ocytes. PPAR mRNA levels were not regulated by Zileuton. In a first pilot clinical study with 10 patients with papulopustular acne Zileuton 4 x 600 mg/d p.o. for 3 months decreased the acne severity index in a time-dependent manner being 41% of the initial score at week 12 (p < 0.05). This was mostly due to a decrease of the number of inflammatory lesions of 29% (p < 0.01). In addition, total sebum lipids significantly decreased (35%, p < 0.05) and the pro-inflammatory free fatty acids (22%) and lipoperoxides (26%) were markedly diminished in patients' sebum under treatment. The magnitude of clinical improvement strongly correlated with the reduction of total sebum lipids (p = 0.0009, r(2) = 0.81) and free fatty acids (p = 0.0003, r(2) = 0.82). In a further study, a 40-year-old female with mild disseminated sebaceous gland hyperplasia and seborrhea, responded with normalization of the casual skin surface lipids and similar reduction of facial sebum synthesis under treatment with Zileuton over 2weeks and-after a wash-out phase-low-dose isotretinoin (10 mg/2nd d) over 5 weeks. These data are in agreement with a phase II multicenter, clinical study in 101 patients with mild to moderate inflammatory facial acne conducted in the US, which showed a significant efficacy of Zileuton in a subset of patients with moderate acne, whereas those patients treated with Zileuton showed a significant mean decrease in inflammatory lesions compared to the placebo group. In all clinical studies, Zileuton was found to be safe and well tolerated.
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Acne vulgaris is a common skin condition, one that is associated with significant psychological disability. The psychological impairments in acne include higher rates of depression, anxiety, anger and suicidal thoughts. Despite a paucity of clinical research, patients with skin conditions and/or mental health disorders are frequent consumers of dietary supplements. An overlap may exist between nutrients that potentially have both anti-acne and mood regulating properties; examples include omega-3 fatty acids from fish oil, chromium, zinc and selenium. Here we report on five cases of acne treated with eicosapentaenoic acid and antioxidant nutrients. Self-administration of these nutrients may have improved inflammatory acne lesions and global aspects of well-being; the observations suggest a need for controlled trials.
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Angiogenesis, the development of new blood vessels, is an important process in tissue development and wound healing but becomes pathologic when associated with solid tumor growth, proliferative retinopathies, and rheumatoid arthritis. To date, there has not been a physiologically relevant in vitro model for human angiogenesis that can be used to screen for enhancers and inhibitors of human angiogenesis and allow further investigation of this process. Initially, culture conditions were established for the induction of human angiogenesis in vitro using fragments of human placental blood vessel. Once the assay was validated, it was examined for its ability to detect known inhibitors and enhancers of angiogenesis. The role of endogenous acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) in the angiogenic response was also assessed by performing RT-PCR on both the parent vessel and microvessel outgrowths. In addition, neutralizing antibodies against the three growth factors were used to quantify the relative importance of each growth factor in the angiogenic response. A fragment of human placental blood vessel was embedded in a fibrin gel in microculture plates and was found to give rise to a complex network of microvessels during a period of 7 to 21 days in culture. The response did not require the addition of exogenous growth factors, and thus provides a convenient system for testing substances for their ability to stimulate or inhibit a human in vitro angiogenic response. The ability of the well known angiogenesis antagonist, hydrocortisone, in the presence and absence of heparin, and suramin to significantly inhibit the angiogenic response indicated that the model could be used as an efficient in vitro assay for screening inhibitors of human angiogenesis. The presence of mRNA for aFGF, bFGF, and three isoforms of VEGF, as well as their receptors, FGFR1, FGFR2, Flt-1, and KDR, in vessel outgrowths and the parent vessel, as identified by RT-PCR, strongly implicated aFGF, bFGF, and VEGF as having an important role in this neovascularization response. This was further confirmed by the ability of neutralizing antibodies to aFGF, bFGF, and VEGF to inhibit the angiogenic response to varying extent. Furthermore, the response could be enhanced by the addition of these growth factors in serum-starved cultures. Finally, a stimulatory effect was observed when matrigel was incorporated into the fibrin gel, which indicates that components of the extracellular matrix also play an important role in governing the strength of the angiogenic response. A physiologic angiogenic response relevant to wound healing can be generated by culturing fragments of human placental blood vessels in fibrin gels. The growth factors aFGF, bFGF, and VEGF were shown to play an important role in stimulating this spontaneous angiogenic response. This assay, which can be performed in microcultures, was also shown to be an excellent method for screening for potential inhibitors and enhancers of human angiogenesis.