Indian Journal of Dermatology
  Publication of IADVL, WB
  Official organ of AADV
Indexed with Science Citation Index (E) , Web of Science and PubMed
 
Users online: 4494  
Home About  Editorial Board  Current Issue Archives Online Early Coming Soon Guidelines Subscriptions  e-Alerts    Login  
    Small font sizeDefault font sizeIncrease font size Print this page Email this page


 
Table of Contents 
E-IJD® - ORIGINAL ARTICLE
Year : 2022  |  Volume : 67  |  Issue : 5  |  Page : 624
Assessment of oxidative/nitrosative stress and raftlin in vitiligo


1 Department of Dermatology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey
2 Department of Biochemistry, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey

Date of Web Publication29-Dec-2022

Correspondence Address:
Mehmet K Mulayim
Department of Dermatology, Sutcu Imam University Faculty of Medicine, Avsar Campus, 46100, Onikisubat, Kahramanmaras
Turkey
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_917_20

Rights and Permissions

   Abstract 


Background: Vitiligo is a chronic skin disease characterized by white macules on the skin due to loss of melanocytes. Although there are many theories about the etiopathogenesis of the disease, oxidative stress is identified as an important determinant in the etiology of vitiligo. In recent years, Raftlin has been shown to play a role in many inflammatory diseases. Aims: The aim of this study was to compare the patients with vitiligo and the control group to determine both oxidative/nitrosative stress markers and Raftlin levels. Materials and Methods: This study was designed prospectively between September 2017 and April 2018. Twenty-two patients diagnosed with vitiligo and 15 healthy people as the control group were included in the study. Blood samples collected to determine oxidative/nitrosative stress, the antioxidant enzyme, and Raftlin levels were sent to the biochemistry laboratory. Results: In patients with vitiligo, the activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione S transferase were significantly lower than in the control group (P < 0.0001). In vitiligo patients, the levels of malondialdehyde, nitric oxide, nitrotyrosine (3-NTx), and Raftlin were significantly higher than in the control group (P < 0.0001). Conclusions: The results of the study support that oxidative stress and nitrosative stress may play a role in the pathogenesis of vitiligo. In addition, the Raftlin level, a new biomarker of inflammatory diseases, was found high in patients with vitiligo.


Keywords: Nitrosative stress, oxidative stress, pathogenesis, raftlin, vitiligo


How to cite this article:
Mulayim MK, Kurutas EB, Nazik H, Ozturk P. Assessment of oxidative/nitrosative stress and raftlin in vitiligo. Indian J Dermatol 2022;67:624

How to cite this URL:
Mulayim MK, Kurutas EB, Nazik H, Ozturk P. Assessment of oxidative/nitrosative stress and raftlin in vitiligo. Indian J Dermatol [serial online] 2022 [cited 2023 Feb 7];67:624. Available from: https://www.e-ijd.org/text.asp?2022/67/5/624/366143





   Introduction Top


Vitiligo is a chronic skin disease characterized by the appearance of white macules on the skin, mucosa, and scalp due to the loss of melanocytes. Both sexes are affected equally. Its prevalence ranges from 0.1% to 8.8% worldwide.[1]

The pathogenesis of vitiligo has not yet been fully elucidated. There are different theories to explain the loss of melanocyte activity. These are autoimmune theory, cytotoxic theory, biochemical theory, oxidant-antioxidant theory, viral theory, growth factor theory, chronic pressure theory, nerve theory, genetic theory, and convergence theory.[1],[2]

In recent years, oxidative stress has become prominent in the etiology of vitiligo. An increase in reactive oxygen species (ROS) was observed in the lesional and non-lesional skin of the vitiligo patients.[3] Nitric oxide (NO) and nitrotyrosine (3-NTx) are known as reactive nitrogen species (RNS). Low ROS/RNS levels are required for various biological processes. Increased ROS/RNS formation and/or decreased antioxidant defense may damage cellular components in a process called oxidative/nitrosative stress.[4]

This possible damage of ROS may be prevented by antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S transferase (GST).[5] Lipid peroxidation is one of the most important expressions of ROS-induced oxidative stress. Malondialdehyde (MDA) is an indicator of lipid peroxidation which increases in a variety of diseases.[6] Increased oxidative stress has been proposed as a mechanism that plays a role in the etiopathogenesis of vitiligo by inducing melanocyte destruction due to excessive production of ROS.[7]

One of the major lipid rafts, Raftlin, was first identified in Raji B cells and is essential to the integrity of the lipid rafts. Raftlin has been shown to play an important role in many processes, such as membrane viscosity, signal transduction, and regulation of apoptosis.[8] In addition, Raftlin plays a role in the toll-like receptor 3 activation and autoimmune response.[9] The role of lipid raft in the pathophysiology of inflammatory responses led to our assumption that Raftlin may play a role in the pathogenesis of vitiligo.

As far as we know, although there are studies on oxidative stress in vitiligo, there is no study in which both oxidative stress and nitrosative stress are studied and the Raftlin level is examined. This study aims to compare oxidative/nitrosative stress markers (MDA/NO and 3-NTx), antioxidant (SOD, CAT, GPx, and GST) response levels and Raftlin levels, a new biomarker in inflammatory diseases, of the vitiligo patients with the control group.


   Materials and Methods Top


Study design

This study was approved by the Scientific and Clinical Researches Ethics Committee of the Kahramanmaras Sutcu Imam University Medical Faculty. The legal guardians of those under the age of 18 and all subjects who were included in the study provided informed written consent.

The study included 22 patients who attended the dermatology outpatient clinic of the Kahramanmaras Sutcu Imam University Medical Faculty Hospital between September 2017 and April 2018 and were diagnosed with vitiligo by clinical examination and Wood's lamp examination. All of the patient groups were non-segmental vitiligo patients. Patients who used systemic or topical treatment at least 1 month before starting the study were excluded from the study. Fifteen healthy people without any systemic or dermatological diseases were included as the control group. There was no family history of vitiligo in the first- and second-degree relatives of the healthy controls. There was no smoking, alcohol use, or any medication use in the patient and control groups. Calculating with GPower 3.1 (http://www.gpower.hhu.de/) gives a power of 80% with alpha = 0.05 when comparing the two means using student t test with a total sample size of 18 patients (patient/control: 9/9).

Biochemical analysis

Blood samples were taken from 22 patients and 15 control individuals. The samples were centrifuged at 3000 g for 10 min at 4°C. The plasma was separated and the buffy coat was discarded by aspiration. The erythrocytes were washed four times with cold physiological saline solution and stored at −70°C until analysis. The CAT activity in the erythrocyte was measured in samples by the method applied by Beutler.[10] The decomposition of the substrate hydrogen peroxide was monitored spectrophotometrically at 240 nm. The activity of CAT was expressed as U/g Hb. The SOD activities in the erythrocyte were estimated using the method described by Fridovich.[11] The SOD activity was expressed as U/g Hb. The GST activity was measured spectrophotometrically at 340 nm by the method of Habig et al.[12] with 1-Chloro-2,4-dinitrobenzene as a substrate. GST was calculated as U/g Hb. The lipid peroxidation level in the plasma samples was expressed in MDA. The measurement was based on the method of Ohkawa.[13] The MDA levels were expressed as nmol/mL. NO, 3-NTx, and the Raftlin levels in the plasma samples were determined with sandwich enzyme linked immunosorbent assay kits (MyBioSource human ELISA kits, USA), according to the manufacturers' protocol. The 3-NTx levels were given as nmol/L.

Statistical analysis

The SPSS 22.0 (SPSS, Chicago, IL) software package was used to evaluate the data obtained in the study. Continuous data were summarized as mean and standard deviation while categorical data were summarized as counts and percentages. The Chi-square test was used for categorical variables and the Mann–Whitney U test for numerical variables. The receiver operating characteristic (ROC) curve was used to investigate the accuracy of Raftlin, CAT, SOD, MDA, GPx, GST, NO, and 3-NTx in indicating vitiligo. To investigate the accuracy of the test, sensitivity, specificity, and 95% confidence intervals were calculated and presented in a tabular form. Any P values below 0.05 were considered statistically significant.


   Results Top


A total of 37 cases, namely 22 (59.5%) patients with vitiligo and 15 (40.5%) control groups, were included in the study. Within the vitiligo group, 45.5% (n = 10) of the patients were female and 54.5% (n = 12) were male. Within the control group, 53.3% (n = 8) of the individuals were female and 46.7% (n = 7) were male. The mean ages of the vitiligo group and the control group were 35.6 ± 16.8 years (min-max: 10–65 years) and 29.6 ± 9.2 years (min-max: 17–47 years), respectively. There was no statistically significant difference between the groups regarding gender and age (the P values were 0.222 and 0.435, respectively).

The median, minimum, and maximum values of Raftlin, CAT, SOD, MDA, GPx, GST, NO, and 3-NTx of the patient and the control groups are shown in [Table 1].
Table 1: Median, minimum, and maximum values of Raftlin, CAT, SOD, MDA, GPx, GST, NO, and 3-NTx of the patient and control groups

Click here to view


The mean standard deviation of the Raftlin values was statistically significantly higher in the vitiligo group (P < 0.0001) (ROC curve analysis for Raftlin is presented graphically in [Figure 1]). The mean standard deviation of the CAT values was statistically significantly lower in the vitiligo group (P < 0.0001). The mean standard deviation of the SOD values was statistically significantly lower in the vitiligo group (P < 0.0001). The mean standard deviation of the MDA values was statistically significantly higher in the vitiligo group (P < 0.0001) (ROC curve analysis for MDA is presented graphically in [Figure 2]). The mean standard deviation of the GPx values was statistically significantly lower in the vitiligo group (P < 0.0001). The mean standard deviation of the GST values was statistically significantly lower in the vitiligo group (P < 0.0001). The mean standard deviation of the NO values was statistically significantly higher in the vitiligo group (P < 0.0001) (ROC curve analysis for NO is presented graphically in [Figure 3]). The mean standard deviation of the 3-NTx values was statistically significantly higher in the vitiligo group (P < 0.0001) (ROC curve analysis for 3-NTx is presented graphically in [Figure 4]).
Figure 1: ROC curve for Raftlin area under the curve value of 0.979

Click here to view
Figure 2: ROC curve for malondialdehyde area under the curve value of 1.0

Click here to view
Figure 3: ROC curve for nitric oxide area under the curve value of 0.982

Click here to view
Figure 4: ROC curve for nitrotyrosine area under the curve value of 0.997

Click here to view


While the CAT, SOD, GPx, and GST values were significantly lower, Raftlin, MDA, NO, and 3-NTx values were significantly higher in the vitiligo group compared with the control group. The cut-off, sensitivity, specificity, and area under the curve (AUC) values of Raftlin, MDA, NO, and 3-NTx, which are found to be statistically significant in indicating vitiligo, are given in [Table 2]. In this table, markers with AUC values below 0.5 (CAT, SOD, GPx, and GST) were not used.
Table 2: Cut-off, sensitivity, specificity, AUC, 95% CI, and P values of Raftlin, MDA, NO, and 3-NTx in indicating vitiligo

Click here to view



   Discussion Top


The etiology and pathogenesis of vitiligo remain unclear. Understanding etiopathogenesis may help prevent treatment failure and find new treatment modalities. Although there are many theories about the etiopathogenesis of vitiligo, there is strong evidence that oxidative stress plays a pivotal role in the onset and progression of the disease.[14]

As far as we know, this study is the first study measuring both oxidative/nitrosative stress markers such as SOD, CAT, MDA, GPx, GST, NO, and 3-NTx, as well as Raftlin levels, a new biomarker of inflammatory diseases, in patients with vitiligo. The results of our study show that both oxidative stress and nitrosative stress are increased and Raftlin levels are enhanced in vitiligo.

Both oxidative and nitrosative stress are associated with the formation of free radicals. In 1956, Denham Harman, an American gerontologist, first described free radicals as compounds involved in processes that lead to cell damage, mutagenesis, tumor development, and biological aging. Free radical production in the cell occurs continuously during metabolism. These radicals, ROS (such as superoxide anion, hydroxyl radical, and hydrogen peroxide) and RNS (such as, NO and peroxynitrite anion), are highly reactive and therefore potentially harmful biomolecules.[15] ROS and RNS are essential for physiological processes such as signal transduction, gene transcription, and host defense but are also associated with pathological conditions. Cellular oxygen is highly reactive and is reduced to less reactive hydrogen peroxide via the SOD enzyme, which is reduced to water and oxygen by the CAT enzyme. In addition, ROS is neutralized by enzymes such as, GPx and GST. Therefore, the measurement of levels and/or enzymatic activity of SOD, CAT, GPx, and GST are an useful indicator of cellular oxidative stress.[4],[16]

Different research groups have reported conflicting results regarding SOD, CAT, GPx, GST, NO, 3-NTx, and MDA levels in vitiligo patients. Passi et al.[17] showed that oxidative stress causes damage to epidermal cells and suggested that antioxidant therapy may play a role in the treatment of vitiligo.

Arican et al.[6] and Yildirim et al.[18] reported that the SOD activity in the erythrocytes was significantly higher in patients with vitiligo than in the control group. Dell'Anna et al.[19] found higher SOD activity in the leukocytes of vitiligo patients. Similarly, Maresca et al.,[20] Hazneci et al.,[21] Jain et al.,[22] and Ozel Turkcu et al.[23] observed that blood SOD activity was significantly higher in vitiligo patients than in healthy controls. Taştan et al.[24] reported that there was no statistically significant difference in the SOD activity between the lesional tissue and the non-lesional tissue in vitiligo patients. However, Koca et al.[25] showed that the SOD activity in the blood of patients with vitiligo is lower than in the control group. In our study, the SOD activity in the erythrocytes was statistically significantly lower in patients with vitiligo than in the control group. We believe that the discrepancies observed in the results may be associated with differences in serum, leukocyte, erythrocyte and epidermis levels, duration and activity of the disease, and differences in laboratory techniques.

Many studies on the effectiveness of CAT enzyme activity in vitiligo have been carried out in tissue, blood, and serum. Liu et al.,[1] Maresca et al.,[20] and Ozel Turkcu et al.[23] observed that the patients with vitiligo have lower serum CAT activity than the control group. Dell'Anna et al.[19] reported that the CAT activity is low in the leukocytes of vitiligo patients. Arican et al.[6] reported that the CAT activity is low in the erythrocytes of localized vitiligo patients. Low CAT activity was observed in the lesional and normal skin of segmental vitiligo, as well as in the cultured melanocytes, leading to the accumulation of epidermal hydrogen peroxide.[17],[20] Hazneci et al.[21] and Sravani et al.[26] reported that the CAT activity is low in the skin and blood of vitiligo patients. Schallreuter et al.[27] found decreased CAT activity in the affected and unaffected skin of vitiligo patients. In line with other studies, the CAT activity in patients with vitiligo was also statistically significantly lower than in the control group in our study.

ROS is neutralized by GPx in a reaction that converts cellular antioxidant glutathione from its reduced state to its oxidized form.[4] In studies of vitiligo mouse models, it was found that GPx, SOD, and CAT enzyme activities that clear free oxygen radicals causing oxidative stress were low.[28] A study reported that in patients with vitiligo up to the age of 46, the GPx activity was lower compared with the control group, while there was no significant difference in the vitiligo group after the age of 46 compared with the control group.[29] Jalel et al.[30] showed that patients with vitiligo have low GPx enzyme activity. In accordance with other studies, in our study, the GPx activity in the erythrocytes was statistically significantly lower in vitiligo patients than in the control group.

GST consists of isoenzymes involved in the defense mechanisms against oxidative stress. GST may detoxify various compounds produced by damage to cells caused by ROS.[5] Liu et al.[5] reported that the absence of the GST gene (especially the GST-T1 and M1 genes) could be a risk factor for vitiligo. In our study, the GST activity in the erythrocytes was also statistically significantly lower in vitiligo patients than in the control group.

MDA is a product of ROS-induced lipid peroxidation and is considered a specific indicator of oxidative stress.[6] Picardo et al.[31] and Tastan et al.[24] found that MDA levels are normal in the erythrocytes of vitiligo patients. Arican et al.,[6] Yıldırım et al.,[18] and Koca et al.[25] showed that serum MDA levels were high in vitiligo patients. In another study, the MDA level was reported to be high in the tissues of patients with vitiligo.[32] Laddha et al.[33] reported the importance of oxidative stress and high lipid peroxidation levels in vitiligo patients. In accordance with other studies, in our study, the MDA level in the vitiligo group was also statistically significantly higher than in the control group. In addition, our study shows that the MDA level has an auxiliary diagnostic value for vitiligo with high sensitivity and specificity compared with the ROC curve analysis.

The results of our study support that oxidative stress may play a role in the etiopathogenesis of vitiligo due to both decreased activity of antioxidant enzymes such as, SOD, CAT, GPx, and GST and increased MDA levels which indicate lipid peroxidation due to oxidative stress.

Like ROS, RNS may play an important role in the pathogenesis of various diseases. The most important markers of nitrosative stress are NO and 3-NTx.[34] Low NO levels generally have a beneficial effect and protect against cell death. High NO levels may damage cellular components and induce apoptosis.[35] A study showed that NO-induced apoptosis may be the reason for the decrease in the number of melanocytes in vitiligo.[36] It has been stated that NO may cause skin depigmentation by causing auto-destruction of melanocytes in cultured human melanocytes.[37] Yildirim et al.[18] reported that the NO level in erythrocytes increased significantly in patients with vitiligo compared with the control group. Another study reported that there was no statistically significant difference between the NO levels in the tissue of patients with vitiligo and the NO levels of the healthy control group.[32] In our study, the NO level in the vitiligo group was statistically significantly higher than in the control group. In addition, our study shows that the NO level is an auxiliary diagnostic value for vitiligo with high sensitivity and specificity compared with the ROC curve analysis.

The 3-NTx is a characteristic marker of nitrosative stress and a common mark of inflammation. NO and 3-NTx levels have been reported to be high in various skin diseases such as, skin cancers, systemic lupus erythematosus, psoriasis, urticaria, and atopic dermatitis.[38] In addition, levels of 3-NTx have been shown to increase in the tissue with vitiligo.[39] Another study emphasized that 3-NTx may play a role in the pathogenesis of vitiligo due to its effects on mitochondrial Deoxyribonucleic acid (DNA).[40] In our study, the 3-NTx level in the vitiligo group was statistically significantly higher than in the control group. Furthermore, our study shows that the 3-NTx level is an auxiliary diagnostic value for vitiligo with high sensitivity and specificity compared with the ROC curve analysis.

Our study showed that nitrosative stress is increased in vitiligo as a result of high NO and 3-NTx levels in vitiligo patients. This supports that nitrosative stress may play a role in the etiopathogenesis of vitiligo.

Membrane microdomains known as lipid rafts have been shown to act as platforms for the initiation of various receptor signals. Saeki et al.[8] described a new protein called Raftlin (raft-linking protein) as a major protein in lipid rafts. The Raftlin B cell identified in Raji B cells is responsible for regulating the signal transmission of antigen receptors.[8] It was shown that Raftlin modulates the signals of T cell receptors and is also necessary for fine-tuning T cell-mediated immune responses. It has also been shown that excessive Raftlin expression may play a role in the development or progression of T cell-mediated immune diseases.[41] Apart from lipid rafts in B and T cells, Raftlin is also localized in the cytoplasm of human epithelial cells.[42] Tatematsu et al.[42] showed that Raftlin plays a role in both innate and adaptive immunity depending on the cell type.

There is a limited number of studies on Raftlin. As far as we know, there is no similar study conducted in vitiligo patients and therefore, we could not compare our results with those of others. However, some studies on Raftlin have reported that Raftlin plays a possible role in neuronal degeneration in Alzheimer's disease.[43] Lee et al.[44] stated that the level of Raftlin in septic patients is associated with the severity of sepsis and may represent a new marker of endothelial cell dysfunction. The authors also stated that Raftlin may be used as a biomarker to determine the severity of sepsis. Ozer et al.[45] observed that Raftlin levels were significantly higher in patients with appendicitis than in healthy controls and stated that Raftlin may be a new diagnostic parameter that may be used in inflammatory diseases. Bilgen et al.[46] studied Raftlin levels in wound healing and showed that the levels of Raftlin in tissue were significantly higher in patients with a wound than in the control group.

In our study, the Raftlin level was statistically significantly higher in the vitiligo group than in the control group. Moreover, our study shows that the level of Raftlin is an auxiliary diagnostic value for vitiligo with high sensitivity and specificity compared with the ROC curve analysis.

We believe that there is melanocyte destruction in vitiligo because of free radical-mediated inflammation due to oxidative stress and nitrosative stress and Raftlin levels increase due to this inflammation. Raftlin may be a new biomarker in the demonstration of inflammatory diseases such as vitiligo. However, new studies including larger series are warranted on this subject.

Limitations

The first is that this study had limited number of patients. Another important limitation is the absence of posttreatment oxidative/nitrosative stress markers and Raftlin levels due to the cross-sectional design of the study.


   Conclusion Top


We can suggest that oxidative and nitrosative stress may play a role in the pathogenesis of vitiligo by causing melanocyte damage. Therefore, we suggest that additional treatments containing antioxidants may be beneficial in vitiligo patients to reduce oxidative stress and nitrosative stress. Furthermore, our results may be considered as a preliminary study for studies with larger populations and pre/posttreatment values to determine the role of Raftlin in vitiligo etiopathogenesis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This study was financially supported by the Kahramanmaras Sutcu Imam University Scientific Research Project unit (Project No.: 2016/3-60 M).

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Liu L, Li C, Gao J, Li K, Zhang R, Wang G, et al. Promoter variant in the catalase gene is associated with vitiligo in Chinese people. J Invest Dermatol2010;130:2647-53.  Back to cited text no. 1
    
2.
Njoo MD, Westerhof W. Vitiligo. Pathogenesis and treatment. Am J Clin Dermatol 2001;2:167-81.  Back to cited text no. 2
    
3.
Delmas V, Larue L. Molecular and cellular basis of depigmentation in vitiligo patients. Exp Dermatol2019;28:662-6.  Back to cited text no. 3
    
4.
Abrahams S, Haylett WL, Johnson G, Carr JA, Bardien S. Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: A review. Neuroscience2019;406:1-21.  Back to cited text no. 4
    
5.
Liu L, Li C, Gao J, Li K, Gao L, Gao T. Genetic polymorphisms of glutathione S-transferase and risk of vitiligo in the Chinese population. J Invest Dermatol2009;129:2646-52.  Back to cited text no. 5
    
6.
Arican O, Kurutas EB. Oxidative stress in the blood of patients with active localized vitiligo. Acta Dermatovenerol Alp Pannonica Adriat 2008;17:12-6.  Back to cited text no. 6
    
7.
Speeckaert R, Speeckaert MM, van Geel N. Why treatments do(n't) work in vitiligo: An autoinflammatory perspective. Autoimmun Rev2015;14:332-40.  Back to cited text no. 7
    
8.
Saeki K, Miura Y, Aki D, Kurosaki T, Yoshimura A. The B cell-specific major raft protein, Raftlin, is necessary for the integrity of lipid raft and BCR signal transduction. EMBO J2003;22:3015-26.  Back to cited text no. 8
    
9.
Watanabe A, Tatematsu M, Saeki K, Shibata S, Shime H, Yoshimura A, et al. Raftlin is involved in the nucleocapture complex to induce poly (I: C)-mediated TLR3 activation. J Biol Chem2011;286:10702-11.  Back to cited text no. 9
    
10.
Beutler E, editor. Red Cell Metabolism: A Manual of Biochemical Methods. 2nd ed. New York: Grune and Stratton Inc; 1984.  Back to cited text no. 10
    
11.
Fridovich I. Superoxide dismutase. Adv Enzymol1974;41:35-97.  Back to cited text no. 11
    
12.
Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130-9.  Back to cited text no. 12
    
13.
Ohkawa H, Ohishi N, Tagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.  Back to cited text no. 13
    
14.
Denat L, Kadekaro AL, Marrot L, Leachman SA, Abdel-Malek ZA. Melanocytes as instigators and victims of oxidative stress. J Invest Dermatol 2014;134:1512-8.  Back to cited text no. 14
    
15.
Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 2002;82:47-95.  Back to cited text no. 15
    
16.
Maia A, Oliveira J, Lajnef M, Mallet L, Tamouza R, Leboyer M, et al. Oxidative and nitrosative stress markers in obsessive-compulsive disorder: A systematic review and meta-analysis. Acta Psychiatr Scand 2019;139:420-33.  Back to cited text no. 16
    
17.
Passi S, Grandinetti M, Maggio F, Stancato A, De Luca C. Epidermal oxidative stress in vitiligo. Pigment Cell Res 1998;11:81-5.  Back to cited text no. 17
    
18.
Yildirim M, Baysal V, Inaloz HS, Kesici D, Delibas N. The role of oxidants and antioxidants in generalized vitiligo. J Dermatol 2003;30:104-8.  Back to cited text no. 18
    
19.
Dell'Anna ML, Maresca V, Briganti S, Camera E, Falchi M, Picardo M. Mitochondrial impairment in peripheral blood mononuclear cells during the active phase of vitiligo. J Invest Dermatol 2001;117:908-13.  Back to cited text no. 19
    
20.
Maresca V, Roccella M, Roccella F, Camera E, Del Porto G, Passi S, et al. Increased sensitivity to peroxidative agents as a possible pathogenetic factor of melanocyte damage in vitiligo. J Invest Dermatol 1997;109:310-3.  Back to cited text no. 20
    
21.
Hazneci E, Karabulut AB, Ozturk C, Batçioğlu K, Doğan G, Karaca S, et al. A comparative study of superoxide dismutase, catalase, and glutathione peroxidase activities and nitrate levels in vitiligo patients. Int J Dermatol 2005;44:636-40.  Back to cited text no. 21
    
22.
Jain A, Mal J, Mehndiratta V, Chander R, Patra SK. Study of oxidative stress in vitiligo. Indian J Clin Biochem 2011;26:78-81.  Back to cited text no. 22
    
23.
Ozel Turkcu U, Solak Tekin N, Gokdogan Edgunlu T, Karakas Celik S, Oner S. The association of FOXO3A gene polymorphisms with serum FOXO3A levels and oxidative stress markers in vitiligo patients. Gene 2014;536:129-34.  Back to cited text no. 23
    
24.
Taştan HB, Erol IE, Sayal A, Erbil AH. Vitiligoda eser element ve attioksidan düzeyleri. T Klin J Dermatol 2003;13:141-9.  Back to cited text no. 24
    
25.
Koca R, Armutcu F, Altinyazar HC, Gurel A. Oxidant-antioxidant enzymes and lipid peroxidation in generalized vitiligo. Clin Exp Dermatol 2004;29:406-9.  Back to cited text no. 25
    
26.
Sravani PV, Babu NK, Gopal KV, Rao GR, Rao AR, Moorthy B, et al. Determination of oxidative stress in vitiligo by measuring superoxide dismutase and catalase levels in vitiliginous and non-vitiliginous skin. Indian J Dermatol Venereol Leprol 2009;75:268-71.  Back to cited text no. 26
[PUBMED]  [Full text]  
27.
Schallreuter KU, Wood JM, Berger J. Low catalase levels in the epidermis of patients with vitiligo. J Invest Dermatol 1991;97:1081-5.  Back to cited text no. 27
    
28.
Jalel A, Yassine M, Hamdaoui MH. Oxidative stress in experimental vitiligo C57BL/6 mice. Indian J Dermatol 2009;54:221-4.  Back to cited text no. 28
[PUBMED]  [Full text]  
29.
Beazley WD, Gaze D, Panske A, Panzig E, Schallreuter KU. Serum selenium levels and blood glutathione peroxidase activities in vitiligo. Br J Dermatol 1999;141:301-3.  Back to cited text no. 29
    
30.
Jalel A, Hamdaoui MH. Study of total antioxidant status and glutathione peroxidase activity in Tunisian vitiligo patients. Indian J Dermatol 2009;54:13-6.  Back to cited text no. 30
[PUBMED]  [Full text]  
31.
Picardo M, Passi S, Morrone A, Grandinetti M, Di Carlo A, Ippolito F. Antioxidant status in the blood of patients with active vitiligo. Pigment Cell Res 1994;7:110-5.  Back to cited text no. 31
    
32.
Yildirim M, Baysal V, Inaloz HS, Can M. The role of oxidants and antioxidants in generalized vitiligo at tissue level. J Eur Acad Dermatol Venereol 2004;18:683-6.  Back to cited text no. 32
    
33.
Laddha NC, Dwivedi M, Gani AR, Shajil EM, Begum R. Involvement of superoxide dismutase isoenzymes and their genetic variants in progression of and higher susceptibility to vitiligo. Free Radic BiolMed 2013;65:1110-25.  Back to cited text no. 33
    
34.
Al-Shobaili HA, Alzolibani AA, Al Robaee AA, Meki AR, Rasheed Z. Biochemical markers of oxidative and nitrosative stress in acne vulgaris: Correlation with disease activity. J Clin Lab Anal 2013;27:45-52.  Back to cited text no. 34
    
35.
Peter D, Amirtharaj GJ, Mathew T, Pulimood S, Ramachandran A. Role of oxidative and nitrosative stress in pathophysiology of toxic epidermal necrolysis and Stevens Johnson Syndrome-A pilot study. Indian J Dermatol 2015;60:427-31.  Back to cited text no. 35
[PUBMED]  [Full text]  
36.
Ivanova K, Le Poole IC, Gerzer R, Westerhof W, Das PK. Effect of nitric oxide on the adhesion of human melanocytes to extracellular matrix components. J Pathol 1997;183:469-76.  Back to cited text no. 36
    
37.
Rocha IM, Guillo LA. Lipopolysaccharide and cytokines induce nitric oxide synthase and produce nitric oxide in cultured normal human melanocytes. Arch Dermatol Res 2001;293:245-8.  Back to cited text no. 37
    
38.
Kurutas EB, Ozturk P. The evaluation of local oxidative/nitrosative stress in patients with pityriasis versicolor: A preliminary study. Mycoses 2016;59:720-5.  Back to cited text no. 38
    
39.
Salem MM, Shalbaf M, Gibbons NC, Chavan B, Thornton JM, Schallreuter KU. Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: A possible repair mechanism for DNA damage. FASEB J 2009;23:3790-807.  Back to cited text no. 39
    
40.
Al-Shobaili HA, Rasheed Z. Mitochondrial DNA acquires immunogenicity on exposure to nitrosative stress in patients with vitiligo. Hum Immunol 2014;75:1053-61.  Back to cited text no. 40
    
41.
Saeki K, Fukuyama S, Ayada T, Nakaya M, Aki D, Takaesu G, et al. A major lipid raft protein raftlin modulates T cell receptor signaling and enhances th17-mediated autoimmune responses. J Immunol 2009;182:5929-37.  Back to cited text no. 41
    
42.
Tatematsu M, Yoshida R, Morioka Y, Ishii N, Funami K, Watanabe A, et al. Raftlin controls lipopolysaccharide-ınduced TLR4 ınternalization and TICAM-1 signaling in a cell type-specific manner. J Immunol 2016;196:3865-76.  Back to cited text no. 42
    
43.
Wollmer MA, Sleegers K, Ingelsson M, Zekanowski C, Brouwers N, Maruszak A, et al. Association study of cholesterol-related genes in Alzheimer's disease. Neurogenetics 2007;8:179-88.  Back to cited text no. 43
    
44.
Lee W, Yoo H, Ku SK, Kim SW, Bae JS. Raftlin: A new biomarker in human sepsis. Inflammation 2014;37:706-11.  Back to cited text no. 44
    
45.
Ozer OF, Guler EM, Kocyigit A, Selek S, Yigit M, Meral I, et al. Raftlin, presepsin levels and thiol-disulphide homeostasis in acute appendicitis: A pilot study. J Pak Med Assoc 2018;68:1660-5.  Back to cited text no. 45
    
46.
Bilgen F, Ural A, Kurutas EB, Bekerecioglu M. The effect of oxidative stress and Raftlin levels on wound healing. Int Wound J 2019;16:1178-84.  Back to cited text no. 46
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
Print this article  Email this article
 
 
  Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (670 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed376    
    Printed8    
    Emailed0    
    PDF Downloaded9    
    Comments [Add]    

Recommend this journal