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Oxidative stress and alopecia areata

Authors:

Abstract

Alopecia areata (AA) is an inflammatory and autoimmune disease presenting with non-scarring hair loss. The aethiopathogenesis of alopecia areata is unclear and many factors including autoimmunity, genetic predisposition, emotional and environmental stress are thought to play important roles in its development. Antioxidant/ oxidant balance perturbation is a common feature in autoimmune, emotional and environmental stress. Therefore, our paper discusses the implications of oxidative stress in alopecia areata. Abbreviations: AA = alopecia areata, ROS = reactive oxygen species, H2O2 = hydrogen peroxide, TBARS = thiobarbituric acid rective substances, MDA = malondialdehyde, TBARS = thiobarbituric acid-reactive substances, SOD = superoxide dismutase, CAT = catalase, GSH-Px = glutathione peroxidase, PON1 = paraoxonase 1, HO-1 = hemoxigenase 1, TrxR = thioredoxin reductase, GSH = glutathione
Journal of Medicine and Life Vol. 8, Special Issue, 2015, pp.43-46
Oxidative stress and alopecia areata
Prie BE*, Voiculescu VM* **, Ionescu-Bozdog OB***, Petrutescu B****, Iosif L* *****,
Gaman LE* *****, Clatici VG*,**, Stoian I* *****, Giurcaneanu C* **
*”Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
**“Elias” University Emergency Hospital, Bucharest, Romania
***Polimed Clinic, Bucharest, Romania
****Sanmed Medical Center, Bucharest, Romania
*****R&D Irist Labmed, Bucharest, Romania
Correspondence to: Stoian I, MD
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
8 Eroilor Sanitari Blvd., District 5, code 050474, Bucharest, Romania
Mobile phone: +40748 038 284, E-mail: irina_stoian64@yahoo.com
Received: March 5th, 2015 Accepted: June 10th, 2015
Abstract
Alopecia areata (AA) is an inflammatory and autoimmune disease presenting with non-scarring hair loss. The aethiopathogenesis of
alopecia areata is unclear and many factors including autoimmunity, genetic predisposition, emotional and environmental stress are
thought to play important roles in its development. Antioxidant/ oxidant balance perturbation is a common feature in autoimmune,
emotional and environmental stress. Therefore, our paper discusses the implications of oxidative stress in alopecia areata.
Keywords: alopecia areata, oxidative stress, antioxidants
Abbreviations: AA = alopecia areata, ROS = reactive oxygen species, H2O2 = hydrogen peroxide, TBARS = thiobarbituric acid
rective substances, MDA = malondialdehyde, TBARS = thiobarbituric acid-reactive substances, SOD = superoxide dismutase, CAT
= catalase, GSH-Px = glutathione peroxidase, PON1 = paraoxonase 1, HO-1 = hemoxigenase 1, TrxR = thioredoxin reductase, GSH
= glutathione
Introduction
Alopecia areata (AA) is a chronic, inflammatory
and autoimmune disease, presenting with non-scarring
hair loss [1]. AA is a disorder with different clinical
presentations. It most commonly affects the scalp, but any
hair bearing area of the skin can be affected [1]. The hair
loss presents as circumscribed patches (most common),
progression of hair loss and involvement of the entire
scalp (alopecia totalis), or the involvement of the entire
body (alopecia universalis) [2]. Histologically, AA is an
autoimmune disorder with autoaggresive T cells directed
against the anagen hair follicles [3,4]. In the acute stages,
there are abundant inflammatory infiltrates that surround
hair follicles, but the bulb retains its capacity for growth
and follicular stem cells remain viable [4]. The
aethiopathogenesis of AA is unclear and many factors
including the patients genetic constitution, the atopic
state, emotional and environmental stress are claimed to
be involved in its development [1,5,6]
Antioxidant/ oxidant balance perturbation is a
common feature in autoimmune, emotional and
environmental stress. Therefore, our paper discusses the
implications of oxidative stress in AA.
Reactive oxygen species (ROS) and
antioxidant systems
Oxidative stress occurs as a result of inadequate
antioxidant defense or overproduction of free radicals. Its
presence has been shown in many dermatological
diseases including psoriasis [7], vitiligo [8], atopic
dermatitis, lichen planus [9], acne vulgaris [10], pemfigus
vulgaris [11], seborrheic dermatitis [12,13], skin cancers
[14]. The skin is chronically exposed to both endogenous
and environmental pro-oxidant agents leading to the
generation of ROS, which are involved in the damage of
cellular constituents such as nucleic acids, proteins and
cell membrane lipids [15,16].
As a result of permanent oxidative processes,
the body has developed antioxidant defense mechanisms
to prevent the attack of biological molecules [17,18]
Evidence of lipid peroxidation presence in
AA
Lipid peroxidation represents the hallmark of
oxidative stress, which results after cell membrane lipids
are exposed to ROS [17,18]. Lipid peroxides and their
breaking-down products such as malondialdehyde (MDA)
Journal of Medicine and Life Vol. 8, Special Issue, 2015
44
can affect the normal function of most mammalian cells
[15] and their level correlates with the degree of lipid
peroxidation [18].
Several studies evaluated the levels of MDA in
plasma and erythrocytes, but also in scalp biopsies of
patients with AA. Naziroglu et al. found significantly higher
TBARS levels in plasma and erythrocytes of patients with
alopecia than in controls [19]. Akar et al. also found
significantly higher TBARS levels in tissues from scalp
biopsies of patients with AA compared to healthy subjects
and two times higher levels of TBARS in early phase than
late phase of the disease [20]. Koca et al. supported
previous findings and indicated higher levels of serum
MDA in patients with AA compared with control subjects
[18]. Abdel Fattah et al. reported increased levels of MDA
in plasma and tissues. He also noted that the more
severe (polyAA, alopecia totalis, alopecia universalis) and
the longer (≥6 months) the disease, the higher the levels
of MDA [21,22]. Yenin et al. and Bakry et al. also reported
significantly higher levels of MDA in plasma patients with
AA compared with control subjects [17,23].
Enzymatic antioxidants in alopecia areata
Superoxide dismutase (SOD) is the prime
antioxidant enzyme against damage caused by
superoxide anion, converting it to oxygen and hydrogen
peroxide (H2O2) [24,25]. The dysfunction of SOD was
documented in patients with AA [17,18,20,21] and also
that, it can become antigenic if continuously exposed to
ROS and nitrogen species [25]. Akar et al. found elevated
levels of SOD in tissues from scalp biopsies of patients
with AA versus control subjects and two times increased
SOD in early versus late phase of the disease [19]. Abdel
Fattah et al. observed decreased SOD activities and
noted that the more severe (polyAA, alopecia totalis and
alopecia universalis) and the longer (≥ 6 months) the
disease, the lower the levels of SOD [21]. Koca et al. and
Yenin et al. also found decreased SOD activities in serum
and erythrocytes of patients with AA versus control
subjects [18]. Rasheed et al. reported that nitric oxide-
damaged erythrocyte SOD initiate autoantibodies in
patients with AA and also that it may be an important
biomarker for disease progression [25].
Catalase (CAT) inactivates H2O2 via its
dissociation to water and oxygen. Yenin et al. have not
noticed any differences between erythrocyte CAT of
patients with AA versus control subjects [17].
Glutathione peroxidase (GSH-Px) can neutralize
a broad range of peroxides. In the presence of
glutathione, it also converts H2O2 to water and oxygen
[26]. Naziroglu et al. reported that plasma and erythrocyte
GSH-Px was reduced in patients with AA versus controls
[19].
Akar et al. reported a two times increased GSH-
Px activity in tissues from scalp biopsies of patients with
AA than in controls [20]. Yenin et al. noted that
erythrocyte GSH-Px activity was significantly reduced in
patients with AA versus control subjects [17].
Paraoxonase 1 (PON 1) is a Ca-dependent
serum esterase associated with HDL and contributes to
antiatherogenic effects of HDL [27,28]. Lower
paraoxonase activity has been found in serum and tissues
of patients with alopecia areata.
Hemoxigenase-1 (HO-1) is the rate-limiting
enzyme implicated in catabolism of hem with the release
of free irons, carbon monoxide and biliverdin, which is
reduced to bilirubin with antioxidant effects [29]. It has an
important cytoprotective and antioxidant role, limiting skin
inflammation in T cell-dependent inflammatory disorders
and suppressing of antigen presenting cells [30,31]. HO-1
expression was significantly decreased in scalp biopsies
of patients with AA than in control subjects [29].
Thioredoxin reductase (TrxR) is a selenoenzyme
that exerts diverse cellular functions, by reduction of
oxidized thioredoxin in the presence of NADPH [32,33].
Reduced thioredoxin serves as an electron donor for
thioredoxin peroxidase, which reduces H2O2 to water
[33]. The thioredoxin/ thioredoxin reductase system
removes free radicals [34] and the perturbation in TrxR
activity appears in many immunological diseases or
certain malignancies [35]. Sohn et al. reported that the
decrease of TrxR1 may be a cause for glucocorticoid
resistance in AA [32].
Non- enzymatic antioxidants in alopecia areata
Glutathione is a reducing agent with the ability to
neutralize ROS [36]. It is also a cofactor for antioxidant
enzymes [22]. Naziroglu et al. reported decreased levels
of GSH in plasma and erythrocytes of AA patients,
compared with controls [19].
Vitamin E and beta-carotene are essential fat-
soluble vitamins and protectors of the cell membranes
against lipid peroxidation [19], interacting preferentially
with free radicals such as lipid peroxyl radicals [15].
Naziroglu et al. reported significant decrease levels of
beta-carotene in plasma and erythrocytes of AA patients
than in controls, but not a statistically significant degree of
vitamin E [19]. Ramadan et al. also noted lower tissue
and serum vitamine E in AA patients than in controls.
AA therapy and oxidative stress
Medications for AA are still under development.
Treatments thought to reduce oxidative stress are under
consideration based on research studies presenting
evidence of the presence of oxidative stress in alopecia
areata. Administration of a substrate for paraoxonase N-
(3-oxododecanoyl)-L-homoserine-lactone decreased
oxidative stress and stimulated hair growth in ob/ ob mice
[37]. Tempol, a synthetic permeable SOD mimetic
normalized hair growth in a mouse model of chronic
restraint stress [38]. Tocotrienols, antioxidants from
vitamin E, increased hair numbers in volunteers with hair
loss [39]. Interestingly, anthralin, currently used in
Journal of Medicine and Life Vol. 8, Special Issue, 2015
45
alopecia areata treatment exerts its effect via the
generation of free radicals [40].
Conclusion
Although the etiology of AA is still unclear, there
are studies that support the association between oxidative
stress and AA [41]. The conflicting results observed in
some studies can be explained by inclusions criteria and
different stages of the disease considered. The
attenuation of oxidative stress might be a relevant
therapeutic approach and antioxidants can be
recommended as additional drugs in AA treatment [23].
Acknowledgement
This paper is supported by the Sectorial
Operational Programme Human Resources Development
(SOP HRD), financed from the European Social Fund and
by the Romanian Government under the contract
number POSDRU/159/1.5/S/137390.
Disclosures
None
References
1. Alkhalifah A, Alsantali A, Wang E,
McElwee KJ, Shapiro J. Alopecia areata
update. Part I. Clinical picture,
histopathology, and pathogenesis. J. Am.
Acad. Dermatol. 2010; 62:17788.
http://dx.doi.org/10.1016/j.jaad.2009.10.0
32.
2. Yang CC, Chen CC, Chen WC. Aging
and Anti-Aging in Hair and Hair Loss.
Inflammation. Adv. Age Nutr. Res. Clin.
Interv. 2013, Elsevier.
3. Biran R, Zlotogorski A, Ramot Y. The
genetics of alopecia areata: New
approaches, new findings, new
treatments. J. Dermatol. Sci. Japanese
Society for Investigative Dermatology.
2015; 78:1120.
4. Whiting DA. Histopathologic features of
alopecia areata: a new look. Arch.
Dermatol. 2003; 139:15559.
5. Gilhar A, Kalish RS. Alopecia Areata: A
tissue specific autoimmune disease of the
hair follicle. Autoimmun. Rev. 2006; 5:64
9.
6. Barahmani N, Schabath MB, Duvic M.
History of atopy or autoimmunity
increases risk of alopecia areata. J. Am.
Acad. Dermatol. 2009; 61:58191.
7. Bacchetti T, Campanati A, Ferretti G,
Simonetti O, Liberati G, Offidani AM.
Oxidative stress and psoriasis: The effect
of antitumour necrosis factor-α inhibitor
treatment. Br. J. Dermatol. 2013;
168:9849.
8. Akoglu G, Emre S, Metin A, Akbas A,
Yorulmaz A, Isikoglu S et al. Evaluation
of total oxidant and antioxidant status in
localized and generalized vitiligo. Clin.
Exp. Dermatol. 2013; 38:7016.
9. Sapuntsova SG, Lebed’ko OA,
Shchetkina MV, Fleyshman MY,
Kozulin EA, Timoshin SS. Status of
free-radical oxidation and proliferation
processes in patients with atopic
dermatitis and lichen planus. Bull. Exp.
Biol. Med. 2011; 150:6902.
10. Grange PA, Weill B, Dupin N, Batteux
F. Does inflammatory acne result from
imbalance in the keratinocyte innate
immune response?. Microbes Infect.
2010; 12:108590.
11. Yesilova Y, Ucmak D, Selek S,
Dertlioglu SB, Sula B, Bozkus F et al.
Oxidative stress index may play a key role
in patients with pemphigus vulgaris. J.
Eur. Acad. Dermatol. Venereol. 2013;
27:4657.
12. Ozturk P, Arican O, Belge Kurutas E,
Karakas T, Kabakci B. Oxidative stress
in patients with scalp seborrheic
dermatitis. Acta Dermatovenerol. Croat.
2013; 21:805.
13. Emre S, Metin A, Demirseren DD,
Akoglu G, Oztekin A, Neselioglu S et
al. The association of oxidative stress and
disease activity in seborrheic dermatitis.
Arch. Dermatol. Res. 2012; 304:6837.
14. Sander CS, Hamm F, Elsner P, Thiele
JJ. Oxidative stress in malignant
melanoma and non-melanoma skin
cancer. Br. J. Dermatol. 2003; 148:913
22.
15. Briganti S, Picardo M. Antioxidant
activity, lipid peroxidation and skin
diseases. What’s new. J. Eur. Acad.
Dermatol. Venereol. 2003; 17:6639.
16. Bickers DR, Athar M. Oxidative stress in
the pathogenesis of skin disease. J.
Invest. Dermatol. 2006; 126:256575.
17. Yenin JZ, Serarslan G, Yönden Z,
Ulutaş KT. Investigation of oxidative
stress in patients with alopecia areata and
its relationship with disease severity,
duration, recurrence and pattern. Clin.
Exp. Dermatol. 2014; n/a n/a.
18. Koca R, Armutcu F, Altinyazar C, Gürel
A. Evaluation of lipid peroxidation,
oxidant/ antioxidant status, and serum
nitric oxide levels in alopecia areata. Med.
Sci. Monit. 2005; 11:CR296R299.
19. Naziroglu M, Kokcam I. Antioxidants and
lipid peroxidation status in the blood of
patients with alopecia. Cell Biochem.
Funct. 2000; 18:16973.
20. Akar A, Arca E, Erbil H, Akay C, Sayal
A, Gür AR. Antioxidant enzymes and lipid
peroxidation in the scalp of patients with
alopecia areata. J. Dermatol. Sci. 2002;
29:8590.
21. Abdel Fattah NSA, Ebrahim AA, El
Okda ES. Lipid peroxidation/ antioxidant
activity in patients with alopecia areata. J.
Eur. Acad. Dermatology Venereol. 2011;
25:4038.
22. Shah AA, Sinha AA. Oxidative stress
and autoimmune skin disease. Eur. J.
Dermatol. 2013; 23:513.
23. Bakry OA, Elshazly RMA, Shoeib MAM,
Gooda A. Oxidative stress in alopecia
areata: a case-control study. Am. J. Clin.
Dermatol. 2014; 15:5764.
24. Fridovich I. Superoxide anion radical
(O2-.), superoxide dismutases, and
related matters. J. Biol. Chem. 1997;
272:185157.
25. Rasheed Z, Alzolibani AA, Al-Shobaili
HA, Saif GB, Al Robaee AA.
Biochemical and immunological studies
on erythrocytes superoxide dismutase
modified by nitric oxide in patients with
alopecia areata: Implications in alopecia
patchy persistent and alopecia
universalis. Immunol. Lett. 2014; 160:50
7.
26. Brigelius-Flohe R. Tissue-specific
functions of individual glutathione
peroxidases. Free Radic. Biol. Med. 1999;
27:95165.
27. Bilgili SG, Ozkol H, Karadag AS, Ozkol
HU, Seker A, Calka O et al. Serum
paraoxonase activity and oxidative status
in subjects with alopecia areata. Cutan.
Ocul. Toxicol. 2013; 32:2903.
28. Ramadan R, Tawdy A, Abdel Hay R,
Rashed L, Tawfik D. The antioxidant role
of paraoxonase 1 and vitamin E in three
autoimmune diseases. Skin Pharmacol.
Physiol. 2013; 26:27.
29. Yun SJ, Kim H-S, Choi JY, Lee J-B,
Kim S-J, Won YH et al. Decreased heme
oxygenase-1 expression in the scalp of
patients with alopecia areata: the
pathogenic role of heme oxygenase-1. J.
Dermatol. Sci. 2009; 435.
30. Listopad J, Asadullah K, Sievers C,
Ritter T, Meisel C, Sabat R et al. Heme
Journal of Medicine and Life Vol. 8, Special Issue, 2015
46
oxygenase-1 inhibits T cell-dependent
skin inflammation and differentiation and
function of antigen-presenting cells. Exp.
Dermatol. 2007; 16:66170.
31. Wojas-Pelc A, Marcinkiewicz J. What is
a role of haeme oxygenase-1 in
psoriasis?. Current concepts of
pathogenesis. Int. J. Exp. Pathol. 2007;
88:95102.
32. Sohn K-C, Jang S, Choi D-K, Lee Y-S,
Yoon T-J, Jeon EK et al. Effect of
thioredoxin reductase 1 on glucocorticoid
receptor activity in human outer root
sheath cells. Biochem. Biophys. Res.
Commun. 2007; 356:8105.
33. Schallreuter KU, Wood JM. Thioredoxin
reductase - its role in epidermal redox
status. J. Photochem. Photobiol. B. 2001;
64:17984.
34. Zhou Q, Mrowietz U, Rostami-Yazdi M.
Oxidative stress in the pathogenesis of
psoriasis. Free Radic. Biol. Med. 2009;
47:891905.
35. Becker K, Gromer S, Schirmer RH,
Muller S. Thioredoxin reductase as a
pathophysiological factor and drug target.
Eur. J. Biochem. 2000; 267:611825.
36. Townsend DM, Tew KD, Tapiero H. The
importance of glutathione in human
disease. Biomed. Pharmacother. 2003;
57:14555.
37. Minematsu T, Nishijima Y, Huang L,
Nakagami G, Ohta Y, Kurata S et al.
HSL Attenuates the Follicular Oxidative
Stress and Enhances the Hair Growth in
ob/ob Mice. Plast. Reconstr. Surg. Glob.
Open. 2013; 1:e60.
38. Liu N, Wang LH, Guo LL, Wang GQ,
Zhou XP, Jiang Y et al. Chronic
Restraint Stress Inhibits Hair Growth via
Substance P Mediated by Reactive
Oxygen Species in Mice. PLoS One.
2013; 8:1921.
39. Beoy LA, Woei WJ, Hay YK, Pinang P,
Bhd H, Tunku J et al. Effects of
Tocotrienol Supplementation on Hair
Growth in Human Volunteers Scalp hair
plays an important function in humans. In
addition to providing cranial cushioning
and shielding the scalp from direct sun
rays, hair has sociological meanings in
terms. 2010; 21:919.
40. Alkhalifah A, Alsantali A, Wang E,
McElwee KJ, Shapiro J. Alopecia areata
update. Part I. Clinical picture,
histopathology, and pathogenesis. J. Am.
Acad. Dermatol. 2010; 62:17788.
41. Motor S, Ozturk S, Ozcan O, Gurpinar
AB, Can Y, Yuksel R. Evaluation of total
antioxidant status, total oxidant status and
oxidative stress index in patients with
alopecia areata. 2014; 7:108993.
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... Most hair loss is circumscribed patches, but it can also progress to include the entire scalp (alopecia totalis) or involve the entire body (alopecia universalis). Hair loss can manifest in any of these ways (1) . ...
... 10,11 Decrease of DPC activity, or even apoptosis, can lead to hair loss, including AGA. 12 Evidence has revealed that some factors increase the level of oxidative damage in hair follicle, leading to the damage of various substances in the cells of hair follicles, which lead to hair loss. 13,14 Antioxidative capacity of some compounds has been identified as a contributing factor to promote hair growth. ...
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Background Alopecia affects millions of individuals globally, with hair loss becoming more common among young people. Various traditional Chinese medicines (TCM) have been used clinically for treating alopecia, however, the effective compounds and underlying mechanism are less known. We sought to investigate the effect of Alpinetin (AP), a compound extracted from Fabaceae and Zingiberaceae herbs, in hair regeneration. Methods Animal model for hair regeneration was mimicked by depilation in C57BL/6J mice. The mice were then topically treated with 3 mg/ml AP, minoxidil as positive control (PC), or solvent ethanol as vehicle control (VC) on the dorsal skin. Skin color changes which reflected the hair growth stages were monitored and pictured, along with H&E staining and hair shaft length measurement. RNA-seq analysis combined with immunofluorescence staining and qPCR analysis were used for mechanism study. Meanwhile, Gli1 CreERT2 ; R26R tdTomato and Lgr5 EGFP−CreERT2 ; R26R tdTomato transgenic mice were used to monitor the activation and proliferation of Gli1+ and Lgr5+ HFSCs after treatment. Furthermore, the toxicity of AP was tested in keratinocytes and fibroblasts from both human and mouse skin to assess the safety. Results When compared to minoxidil-treated and vehicle-treated control mice, topical application of AP promoted anagen initiation and delayed catagen entry, resulting in a longer anagen phase and hair shaft length. Mechanistically, RNA-seq analysis combined with immunofluorescence staining of Lef1 suggested that Lgr5+ HFSCs in lower bulge were activated by AP via Wnt signaling. Other HFSCs, including K15+, Lef1+, and Gli1+ cells, were also promoted into proliferating upon AP treatment. In addition, AP inhibited cleaved caspase 3-dependent apoptosis at the late anagen stage to postpone regression of hair follicles. More importantly, AP showed no cytotoxicity in keratinocytes and fibroblasts from both human and mouse skin. Conclusion This study clarified the effect of AP in promoting hair regeneration by activating HFSCs via Wnt signaling. Our findings may contribute to the development of a new generation of pilatory that is more efficient and less cytotoxic for treating alopecia.
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We demonstrated enhanced hair regeneration following topical administration of N-(3-oxododecanoyl)-l-homoserine lactone (HSL) in ob/ob mice. The ob/ob mice showed delayed hair regeneration (more than 6 wk) after depilation, which rapidly induced transition to anagen in the hair cycle in wild-type mice. Vehicle and HSL solutions were applied to the depilated dorsal skin of ob/ob mice. The depilated skin of the HSL-treated mice was fully covered with hair, whereas no macroscopic alteration was observed in vehicle-treated group by the fourth week after depilation. Oxidative stress was drastically decreased and the expression of the antioxidative enzymes PON1 and PON3 was increased in the HSL-treated skin with highly proliferative anagen follicles. These results suggest that HSL is a candidate therapeutic agent for alopecia in metabolic syndrome.
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Objectives: In this study, we aimed to evaluate total oxidative stress and total antioxidant capacity in serum samples from patients with Alopesia Areata (AA) in our laboratory conditions. Methods: In this study, 46 subjects with AA (26 females, 20 males) and the control subjects of 36 (20 females, 16 males) age- and sex-matched healthy volunteers from our hospital staffs were enrolled (the mean age was 23.7 ± 11.0 years). Blood samples were obtained following an overnight fasting state, and were collected on ice at 4°C. The serum samples were separated from the cells by centrifugation at 3000 rpm for 15 min and were stored at -80°C and used for the analysis of the Total Antioxidant Status (TAS) and Total Oxidant Status (TOS). Results: Total Antioxidant Status (TAS) and Total Oxidant Status (TOS), Oxidative Stress Index (OSI) (TOS/TAS) levels of AA patients were 1.4777 ± 0.1986; 9.7490 ± 6.0445; 0.6593 ± 0.4069 respectively. TAS; TOS; OSİ (TOS/TAS) levels of controls were 1.4028 ± 0.1687; 9.4627 ± 4.2781; 0.6875 ± 0.3232 respectively. TAS, TOS and OSİ levels showed no significant difference between the control and AA group (p > 0.05). Conclusion: Future studies about AA pathogenesis should be based not only on oxidant/antioxidant balance but also on several other factors. Because it was observed that the disease showed recurrence in different situations. Since the selection criteria of patients is affected from disease severity and environmental and genetical factors, multicentric studies with better sampled patient population and higher patient number is required.
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Purpose of the Study: To investigate the role of paraoxonase 1 (PON1) and vitamin E in the pathogenesis of some autoimmune diseases, and to correlate their levels with the disease activity. Procedures: This randomized case control study was performed on 60 subjects: 45 patients [suffering from psoriasis, vitiligo and alopecia areata (AA) 15 patients each group] and 15 healthy controls. Venous blood and tissue biopsy were collected from each subject to estimate the levels of vitamin E and PON1. Results: All patients showed significantly lower levels of both PON1 and vitamin E in tissue and serum than the controls (p < 0.001). Conclusion: An association between oxidative stress and pathogenesis of these autoimmune diseases is identified. Attenuation of oxidative stress might be a relevant therapeutic approach and it would be useful to recommend additional drugs with antioxidant effects in the treatment of these conditions.
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Alopecia areata (AA) is a common immune-mediated hair loss disorder. Despite its high prevalence, its etiology is still largely unknown, but it is hypothesized to have a strong genetic basis. In the last decade, there has been a major progress in the field of genetic research, leading to novel findings regarding the genetic component of AA. The aim of this review is to summarize the information collected so far in this field, the basic principles of the genetic methods used in previous studies, and new therapeutic strategies that might become available in light of the new findings. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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Background Alopecia areata (AA) is an inflammatory autoimmune disease that causes hair loss on the scalp or trunk without scarring. Although the precise aetiopathogenesis of alopecia areata remains unknown, oxidative stress is thought to play a role.AimTo investigate the relationship between severity and the role of oxidative stress in AA, by measuring plasma oxidant levels and antioxidant enzyme activities in erythrocytes.Methods In total, 62 patients with AA (24 males and 38 females), and 62 sex- and age-matched healthy controls (HCs) were enrolled in the study. We investigated the levels of plasma malondialdehyde (MDA) and the activities of erythrocyte catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The relationship between oxidative stress and AA was also investigated with regard to disease pattern, severity, duration and recurrence.ResultsThe mean erythrocyte GSH-Px and SOD activities were significantly reduced (P < 0.001 and P < 0.001 respectively) compared with the control group. Plasma MDA levels were increased but statistically insignificant (P = 0.08) in patients with AA compared with controls. No significant difference between erythrocyte CAT activities was observed between patients and controls (P = 0.2). In addition, we observed no statistically significant difference in patient plasma MDA levels or erythrocyte CAT, GSH-Px or SOD activities with regard to AA severity, duration, recurrence or pattern (P > 0.05).Conclusions Patients with AA displayed reduced erythrocyte SOD and GSH-Px activities and enhanced plasma MDA levels. These findings support the possible role of oxidative stress in the pathogenesis of AA.
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Alopecia areata (AA) is a non-scarring hair loss disorder that ranges in severity from patchy loss of scalp hair (AA patchy persistent; AAP) to loss of all scalp and body hair (alopecia universalis; AU). The cause of AA is unknown but most evidences support that AA has an autoimmune etiology, where free radicals play an important role. This study was undertaken to investigate the role of nitric oxide (NO) modified erythrocytes superoxide dismutase (eSOD) in AA. Data revealed that NO-induced damage in eSOD caused alteration in hydrophobic or aromatic amino acids and protein carbonyl contents. NO-specific quencher, carboxyl-PTIO further reiterates NO-modifications. Specificity of antibodies from AA patients (n = 26) were analyzed towards NO-modified eSOD (NO-eSOD) and their results were compared with healthy controls (n = 30). Protein-A purified IgG of AA patients (AA-IgG) showed strong binding to NO-eSOD in comparison with IgG from controls. In addition, AA-IgG from patients with AU recognized NO-eSOD in a greater extent as compared to AA-IgG from patients with AAP. Furthermore, AU patients’ sera contained higher levels of NO or carbonyl contents and lower levels of SOD activity compared with AAP patients’ or control sera. In conclusion, this is the first study to demonstrate the role of NO-modified-eSOD in AA. Our novel results conclude that perturbations in SOD by NO presenting unique neo-epitopes that might be one of the factors for the antigen driven antibodies induction in AA. Preferential binding of NO-eSOD by AA-IgG pointed out the likely role of NO-eSOD in the initiation/progression of AA.
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Seborrheic dermatitis (SD) is a common, chronic inflammatory skin disease that mainly affects the scalp. The objective of this study was to evaluate the activities of superoxide dismutase (SOD) and catalase (CAT) and the levels of malondialdehyde (MDA) in scraping samples of patients with scalp SD. Thirty consecutive patients with a diagnosis of scalp SD and thirty-one healthy volunteers were enrolled. The samples were obtained by scraping the skin surface of the scalp. SOD and CAT activities and MDA levels were measured in scraping samples by spectrophotometric method. SOD and CAT activities and MDA levels were significantly higher in patients than in controls (p<0.001 all). There was a positive correlation between the severity of the disease and itching scores (contingency coefficient = 0.671, p<0.001). Except for this correlation, there was no significant correlation among age, sex, duration and severity of the disease, itching scores, antioxidant enzymes and MDA levels in the patient group (p>0.05). Cutaneous oxidative stress in patients with SD may play an important role in the pathogenesis of the disease. Further clinical and laboratory evaluation of the oxidant/antioxidant system in patients with SD is warranted.
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Increased reactive oxygen species (ROS) and lipid peroxidation are seen in many dermatologic disorders, including atopic dermatitis, psoriasis, vitiligo, acne vulgaris, pemphigus vulgaris, and lichen planus. In alopecia areata (AA), there is increased production of ROS from perifollicular inflammatory cells. The aim of this study was to determine the oxidative stress index (OSI) and lipid peroxidation by studying serum total oxidant capacity (TOC), total antioxidant capacity (TAC), and malondialdehyde (MDA) values in AA patients. The study included 35 AA patients and a control group consisting of 30 age- and sex-matched healthy volunteers. The serum TOC, TAC, and MDA values were measured, and the OSIs were calculated and compared in both groups. The mean serum TOC (p < 0.001), MDA (p < 0.001), and OSI (p < 0.001) values were found to be significantly higher in AA patients than in the control group. The mean serum TAC value was significantly lower (p < 0.05) in cases than in controls. Significantly higher MDA (p < 0.001), TOC (p < 0.001), and OSI values (p < 0.001) and lower TAC values (p < 0.01) were found in severe AA than in mild or moderate AA. The demonstrated results confirmed the presence of oxidative stress and lipid peroxidation in AA. Whether these changes play a role in disease pathogenesis or result from the inflammatory process requires further investigation.