There was a significant difference in the advanced glycation end product level between female and male patients with alopecia areata AGEs: Advanced glycation end products, AOPP: Advanced oxidation protein products, FRAP: Ferritin reducing the ability of plasma, PON: Paraoxonase1, LCAT: Lecithin cholesterol acyltransferase, SALT score: the Severity of Alopecia Tool, FBS: fasting blood sugar, LDL: low-density lipoprotein, HDL: high-density lipoprotein, TG: triglyceride, CRP: c-reactive protein.

P -value of less than 0. AGEs: advanced glycation end products, AOPP: advanced oxidation protein products, FRAP: ferritin reducing the ability of plasma, PON: paraoxonase1, LCAT: lecithin cholesterol acyltransferase. The present results revealed that the mean serum levels of markers of oxidative stress were significantly higher in patients with alopecia areata, compared to the controls, whereas the mean antioxidant activity was significantly lower in the alopecia areata group, compared to the controls.

The SALT score and the hair-loss pattern had no significant associations with oxidative and antioxidant markers. Moreover, we found a negative correlation between C-reactive protein and ferric-reducing antioxidant power levels.

C-reactive protein CRP is an inflammatory mediator and was significantly increased in alopecia areata patients. CRP level was not higher in alopecia areata cases. But the possible role of oxidative stress and decreased antioxidative markers like FRAP with inflammatory biomarkers in the development of alopecia areata were indicated.

Generally, it is suggested that oxidative stress plays a critical role in the pathogenesis of autoimmune disorders, including psoriasis, 18 vitiligo 19 and pemphigus vulgaris, 20 by causing inflammation, inducing cell apoptosis, and reducing immune tolerance.

Although some studies have supported the role of oxidative stress in the pathogenesis of alopecia areata, 21 , 22 the results are inadequate and conflicting. There are also reports of increased lipid peroxidation and decreased activities of antioxidants, such as glutathione, glutathione peroxidase, and superoxide dismutase, in patients with alopecia areata, compared to the controls.

found that the mean total antioxidant capacity in the serum was significantly lower in patients with alopecia areata, compared to the controls. On the other hand, Akar et al. found an increase in the antioxidant activity of superoxide dismutase and glutathione peroxidase in the scalp of patients with alopecia areata, especially in the early stages of the disease, whereas no reduction was observed in the lipid peroxidation rate.

Evidence suggests that paraoxonase-1 is significantly reduced in patients with alopecia areata. This enzyme is majorly influenced by gender, as its activity is higher in females than males.

It is known that advanced oxidation protein products and advanced glycation end products activate the membrane receptors for the latter to trigger reactive oxygen species generation and oxidative stress, which is involved in inflammatory diseases.

reported a statistically non-significant higher plasma level of advanced oxidation protein products in patients with alopecia areata compared to the controls; however. The reduced serum levels of lecithin-cholesterol acyltransferase and ferric-reducing antioxidant power have been reported in a wide range of inflammatory diseases, including psoriasis and chronic kidney disease.

Several studies have shown that oxidative stress is involved in the pathogenesis of psoriasis. This study had some limitations. First, the sample size was small.

Second, most correlations, although significant, were weak and difficult to generalise. Therefore, future research with a larger sample size is necessary to confirm our findings.

We were unable to find any previous reports about serum ferric-reducing antioxidant power, lecithin-cholesterol acyltransferase and advanced glycation end-product levels in patients with alopecia areata.

Our results indicated an imbalance of the oxidant-antioxidant enzymatic system in alopecia areata. Therefore, the administration of agents with antioxidant activities may be useful in the management of alopecia areata.

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Share Tweet reddit Share Whatsapp Print Messenger Pinterest Email Viber icon Viber tumblr. Buy Reprints PDF. Brief Report. doi: pmid: PDF Download Citations BibTeX RIS. Department of Dermatology, Imam Khomeini Hospital , Tehran , Iran. Corresponding author: Dr. Safoura Shakoei, Department of Dermatology, Imam Khomeini Hospital, Tehran University of Medical Sciences TUMS , Tehran, Iran.

shakoei gmail. Received: , Accepted: , Epub ahead of print: , Published: © Indian Journal of Dermatology, Venereology and Leprology - Published by Scientific Scholar. Licence This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.

Abstract Background Alopecia areata is a chronic inflammatory skin disease. Aim To evaluate the serum oxidative stress markers and antioxidant capacity in patients with alopecia areata. Methods This cross-sectional study was performed on 40 patients with alopecia areata and 40 healthy controls.

Limitations Since the current study had a cross-sectional design, no cause-effect relationship was established between alopecia areata and oxidative stress. Conclusion Based on the present results, the oxidant-antioxidant enzymatic system is impaired in alopecia areata due to the increased oxidative products and decreased antioxidant activity.

Keywords Alopecia areata advanced glycation end product lecithin-cholesterol acyltransferase oxidative stress PON1. Show Related Articles from PubMed. Plain Language Summary Alopecia areata AA is a chronic inflammatory disease. Introduction Alopecia areata is a common autoimmune skin disorder, with an overall pooled prevalence of 2.

Methods This cross-sectional study was performed on 40 patients with alopecia areata who were treated in outpatient dermatology clinics of Razi and Imam Komeini Hospitals during Results This study was conducted on 40 patients with alopecia areata and 40 healthy controls, including 21 Table 1: Baseline demographics, clinical characteristics and laboratory findings of patients with alopecia areata and healthy controls.

Table 2: Correlations between serum markers and risk factors in AA patients. Table 3: Evaluation of the relationship between involvement pattern and oxidative and antioxidative markers in patients group.

Mean ± SD P -value Patchy Totalis Universalis AGES References Cervantes J , Fertig RM , Maddy A , Tosti A. Alopecia areata of the beard: A review of the literature. Am J Clin Dermatol. Adverse events of non-ablative fractional laser photothermolysis: A retrospective study of treatments in patients.

J Dermatolog Treat. Cwynar A , Olszewska-Slonina D , Czajkowski R , Zegarska B , Bialecka A , Mecinska-Jundzill K , et al. Figure 2 Cumene Hydroperoxide Protects Against Chemotherapy-Induced Alopecia by Activating the P53 Pathway to Arrest Cell Cycle. A RNA-seq heat maps of all differentially expressed genes in control and cumene hydroperoxide-treated rat skin.

B MSigDB Hallmark Molecular Signature Database Hallmark gene enrichment analysis and Gene Ontology of Biological Processes bottom of genes downregulated upon cumene hydroperoxide treatment. C Bar graphs depicting the expression levels of specific genes important for stimulating cell cycle progression in control and treated samples.

Error bars represent the standard deviation of 3 independent replicates. D MSigDB Hallmark gene enrichment analysis of genes upregulated upon cumene hydroperoxide treatment. E Bar graph depicting the expression levels of specific genes implicated in the P53 Pathway left , Apoptosis middle , and Glutathione-mediated Detoxification right in control and treated samples.

F Representative photographic images of VPinduced alopecia in rats that were given no pre-treatment, pre-treatment with low-dose cumene hydroperoxide, with RITA, or with both RITA and low-dose cumene hydroperoxide. The scalp area with a preserved coat of hair is outlined in white. To further investigate the link between cumene hydroperoxide, P53 pathway activation, and cell cycle arrest, we decided to test whether treatment with the P53 activator RITA Reactivation of p53 and Induction of Tumor cell Apoptosis can potentiate the protective effects of cumene hydroperoxide 30 , We therefore pre-treated four groups of six rats with daily subcutaneous injections of either vehicle, low-dose cumene hydroperoxide, RITA µM , or a combination of low-dose cumene hydroperoxide and RITA for six days prior to chemotherapy with VP We found that VP induced total alopecia in all rats pre-treated with either vehicle, low-dose cumene hydroperoxide, or RITA Figure 2F.

However, only the combination of RITA and low-dose cumene hydroperoxide preserved a patch of hair at the site of injection in all six treated rats Figure 2F. Although the protected area of hair is smaller than that of therapeutic levels of cumene hydroperoxide Figure 1A , this result nevertheless shows that co-treatment with the Pactivating RITA enhances the protective effects of low-dose cumene hydroperoxide that is ineffective at preventing alopecia when given alone.

This result thereby provides further evidence to suggest that cumene hydroperoxide protects against chemotherapy-induced alopecia by inducing Pmediated cell cycle arrest in hair follicles.

Chemotherapy-induced alopecia and the appearance of severe hair loss is synonymous with cancer. For many undergoing treatment for cancer, hair loss inflicts significant trauma and represents a major barrier to living a life with normalcy.

Scalp cooling therapy has recently been shown to reduce hair loss in patients receiving chemotherapy. Here, using the rat pup model of chemotherapy-induced alopecia, we showcase a novel proof-of-concept treatment that entirely prevents hair loss induced by many different classes of chemotherapy.

This model has been characterized and validated by previously published studies 27 , Furthermore, the treatment is based on inexpensive peroxides such as cumene hydroperoxide and hydrogen peroxide, the latter being an endogenously occurring and widely available solution found at local pharmacies across the world.

This would therefore remove major barriers for cancer patients to receive treatment for chemotherapy-induced alopecia and would ensure a more equitable access to cancer medical care. Besides our study here, only one other previously published study by Botchkarev et al.

has demonstrated similar levels of in vivo prevention of chemotherapy-induced alopecia However, this was accomplished by deleting P53, which is an important tumor suppressor whose ablation is detrimental to the curative goal of chemotherapy.

Another recent study by Purba et al. This however has not yet been demonstrated in an in vivo model, and the price of Palbociclib would be cost-prohibitive for many patients already undergoing expensive cancer treatments.

Here, we used low-cost cumene hydroperoxide and hydrogen peroxide to generate Pactivating oxidative stress to induce cell cycle arrest, therefore protecting hair follicles from the damaging effects of chemotherapy on actively dividing cells.

A recent study by Chen et al. discovered that scalp cooling protects against chemotherapy-induced alopecia partially via slowing down the cell cycle in hair follicles, making hair follicles resistant to the cytotoxic effects of chemotherapy This therefore serves as an additional line of evidence to show that cell cycle arrest renders hair follicles resistant to cytotoxic chemotherapy.

However, a report from reported a case of oxygen embolism produced by accidental introduction of subcutaneous hydrogen peroxide This suggests that caution should be taken if subcutaneous hydrogen peroxide injections were to be explored further as a modality of therapy.

Nevertheless, based on our observation, no major side effects were observed upon completing the subcutaneous hydrogen peroxide injections. Recent clinical trials have also shown that low-level pain and discomfort are some of the most commonly reported side effects associated with subcutaneous injections Therefore, it may be beneficial for patients to use a topical peroxide preparation.

Future work may explore ways to formulate topical peroxide preparations that can deliver high doses of oxidants subcutaneously. Additionally, existing topical peroxide formulations such as benzoyl peroxide may be explored for its potential in preventing chemotherapy-induced alopecia. The datasets presented in this study can be found in online repositories.

The animal study was reviewed and approved by University of Miami Institutional Animal Care and Use Committee.

JJ conceived the concept of the treatment. JJ designed the experiments with contributions from YZ and JJ performed the experiments and YZ performed the analyses. YZ made the figures and wrote the original draft of the paper. JJ and YZ both contributed to the review and editing.

All authors contributed to the article and approved the submitted version. We would like to thank members of the Dermatopathology Core Laboratory in the Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, particularly Dr.

Carmen I. Perez for support of tissue specimen processing as well as Lucia M. Mauro and Assuan Lens for their technical support and dedication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis 21 3 — doi: PubMed Abstract CrossRef Full Text Google Scholar.

Trüeb RM. Chemotherapy-induced hair loss. Skin Ther Lett 15 7 :5—7. Google Scholar. Choi EK, Kim IR, Chang O, Kang D, Nam SJ, Lee JE, et al. Impact of chemotherapy-induced alopecia distress on body image, psychosocial well-being, and depression in breast cancer patients.

Psychooncology 23 10 — Chemotherapy-induced alopecia. Semin Cutan Med Surg 28 1 —4. Forrest G, Plumb C, Ziebland S, Stein A. Breast cancer in the family—children's perceptions of their mother's cancer and its initial treatment: Qualitative study.

BMJ — Rugo HS, Klein P, Melin SA, Hurvitz SA, Melisko ME, Moore A, et al. Association between use of a scalp cooling device and alopecia after chemotherapy for breast cancer.

JAMA 6 — Nangia J, Wang T, Osborne C, Niravath P, Otte K, Papish S, et al. Effect of a scalp cooling device on alopecia in women undergoing chemotherapy for breast cancer: The SCALP randomized clinical trial. Bajpai J, Kagwade S, Chandrasekharan A, Dandekar S, Kanan S, Kembhavi Y, et al.

Breast — Rugo HS, Voigt J. Scalp hypothermia for preventing alopecia during chemotherapy. A systematic review and meta-analysis of randomized controlled trials.

Clin Breast Cancer 18 1 — Kruse M, Abraham J. Management of chemotherapy-induced alopecia with scalp cooling. J Oncol Pract 14 3 — Yang H, Villani RM, Wang H, Simpson MJ, Roberts MS, Tang M, et al. The role of cellular reactive oxygen species in cancer chemotherapy. J Exp Clin Cancer Res 37 1 Botchkarev VA.

Molecular mechanisms of chemotherapy-induced hair loss. J Investig Dermatol Symp Proc 8 1 —5. Simon HU, Haj-Yehia A, Levi-Schaffer F. Role of reactive oxygen species ROS in apoptosis induction. Apoptosis 5 5 —8.

Haslam IS, Jadkauskaite L, Szabó IL, Staege S, Hesebeck-Brinckmann J, Jenkins G, et al. Oxidative damage control in a human Mini- organ: Nrf2 activation protects against oxidative stress-induced hair growth inhibition.

J Invest Dermatol 2 — Botchkarev VA, Komarova EA, Siebenhaar F, Botchkareva NV, Komarov PG, Maurer M, et al. p53 is essential for chemotherapy-induced hair loss.

A newly released study conducted by Tanacan et al. However, there is no clear evidence that IMA is related to the severity and duration of AA 9.

Malondialdehyde is the end-product of peroxidation reactions caused by ROS acting on lipids. Previous studies have observed the generation of lipid radicals in the skin of mice treated with PPIX plus natural light MDA may be a major product of lipid oxidation and thus an important marker Several studies have measured MDA levels in the plasma and scalp biopsies of AA patients.

Akar et al. Similarly, Cwynar et al. A meta-analysis conducted by Acharya et al. Sachdeva et al. Mustafa et al. However, the results of studies on SOD activity in AA patients are contradictory. In contrast, Yenin et al. Acharya et al. also reported lower serum SOD levels in AA patients than in the control group, while Sachdeva et al.

found significantly decreased whole blood SOD levels in AA patients, with the levels decreasing as the severity of the disease increased 14 , These findings may be explained by the homing of inflammatory cells to AA lesions.

Glutathione peroxidase GSH-Px is an important H 2 O 2 decomposition enzyme widely present in the human body. Yenin et al. The final level of mitochondrial ROS may depend on the activity of MnSOD and GPX1. Genetic differences in antioxidant genes encoding MnSOD and GPX1 may alter the detoxification effect of ROS and increase disease risk Kalkan et al.

The results did not show a statistically significant correlation between clinical and demographic characteristics of alopecia areata patients and MnSOD Ala9Val and GPX1 Pro Leu polymorphic genes, but there was a significant difference between genders Ramadan et al.

Similarly, Dizen-Namdar et al. They also observed significantly higher levels of TOS and lower levels of TAC in patients with AA, indicating an imbalance between oxidative stress and antioxidant capacity.

Vitamin E tocopherol is a major physiological barrier antioxidant A tocopherol molecule can scour two free peroxides and prevent further oxidation of polyunsaturated fatty acids PUFA in cell membranes.

It can also inhibit cyclooxygenase-2 COX2 activity by reducing NO production, thereby reducing prostaglandin E2 PGE2, an important pro-inflammatory mediator. So vitamin E is the most important non-enzymatic antioxidant in the skin Vitamin D regulates the growth and differentiation of hair follicle keratinocytes by binding to the nuclear vitamin D receptor VDR.

It also has anti-inflammatory and immunomodulatory effects 24 , These effects may be related to autoimmunity of alopecia areata. Recent experiments have shown that vitamin D is also an antioxidant Compared with placebo, vitamin D supplementation significantly increased TAC and GSH levels in patients on methadone maintenance therapy an alternative treatment for people addicted to opioid abuse A systematic review and meta-analysis by Lee et al.

In addition to playing a role in enzymatic antioxidant systems, certain metals also contribute to non-enzymatic antioxidant systems. For example, zinc is a crucial component of the SOD enzyme system, while lead is involved in the electron transport chain of ROS.

In a case—control study by Ozaydin-Yavuz et al. This suggests that patients with alopecia areata may have a stronger reactive oxygen production response, leading to the depletion of metal elements required for enzymatic antioxidants in the body. The skin is one of the main barriers between the environment and the body.

It is constantly exposed to a variety of physical and chemical influences and is therefore most directly affected by ROS, which are produced when skin is exposed to visible light or ultraviolet rays Then as a result of the free radical chain reaction, the skin produced lipid, protein, DNA, and other free radicals.

The direct effects of ROS and these free radicals on skin are unclear. However, oxidants produced by ROS, including 4-HNE and MDA, change the structure of proteins, thereby inducing apoptosis and regulating the release of inflammatory cytokines 5.

In addition, ROS could also damage the skin in the following ways: activating transcription factors, upregulating the expression levels of EGF receptor in human keratinocytes 31 , inducing ferroptosis etc.

ROS can trigger and maintain the autoimmune cascade by enhancing cell apoptosis and reducing the efficiency of its clearance, and the resulting accumulation of apoptotic residues promotes the formation of auto-antibodies Elevated levels of endogenous oxidative stress may also be related to disease burden, medication regimen, and duration of treatment, age, and excessive physical and emotional stress associated with comorbid medical conditions Fortunately, there is an antioxidant system in our body to help skin eliminate ROS and free radicals.

The antioxidant system consists of enzymic and non-enzymic antioxidants, which complement and depend on each other to maintain the balance between oxidation and antioxidant. SOD, CAT, and GSH-Px are typical enzymatic antioxidants.

Non-enzymatic antioxidants include vitamin E, vitamin C, vitamin D, GSH, β-carotene, etc. Oxidative stress may be an important trigger for the development of various diseases, such as systemic lupus erythematosus SLE , rheumatoid arthritis RA , and Type 1 diabetes mellitus DM 1.

Resulting from the constant attack of ROS on the skin, oxidative stress has been increasingly investigated as a potential contributor to the development of autoimmune skin diseases, including alopecia areata. The role of oxidative stress in alopecia areata has been increasingly investigated in the recent literature.

As such, investigating the role of oxidative stress in AA is an important area of research that could have implications for treatment and prevention. Collapse of HF-IP is one of the most widely accepted theories about the pathogenesis of alopecia areata.

Collapse of HF-IP may be characterized by upregulation of MHC-I and MHC-II expression 3. As an activator receptor, NKG2D mediates the activation of above immune cells and then kills target cells.

Hsp60, Hsp70, and gp96 can enhance the expression of B7 and MHC-II on the surface of plasmacytoid dendritic cells antigen presenting cells , stimulate dendritic cell maturation, migration to draining lymph nodes, and induce the secretion of chemokines by macrophages and plasmacytoid dendritic cells DCs Studies have shown that IFN-γ secreted by cytotoxic T lymphocytes around vitiligo lesions can up-regulate the expression of Hsp70, and Hsp70 can also enhance the release of IFN-γ by cytotoxic T lymphocytes through a positive feedback mechanism There is a surprising similarity between the pathogenesis of vitiligo and alopecia areata, and the above process may also occurs around the lesions of alopecia areata.

In contrast, IFN-γ -deficient mice were less susceptible to alopecia areata 2. Figure 1. The positive feedback-loop of losing hair follicle-immune privileges and its relationship with oxidative stress. In AA, stimulating factors such as UVB or natural light irradiation can induce the chemotaxis of various inflammatory cells around hair follicular epithelial cells HFECs.

Activated T cells produce IFN-γ via JAK1 and JAK3, and IFN-γ stimulates IL production in HF-ecs via JAK1 and JAK2. IFN-γ and IL-1β are oxidative stress triggers, and IFN-γ is a key player in XO-mediated oxidative stress.

Light irradiation can induce an increase in XO enzyme activity, producing more oxygen free radicals. In addition, skin inflammation caused by UV irradiation synthesized large amounts of ·NO in the presence of the iNOS enzyme.

These ROS can promote the upregulation of NKG2D ligands such as ULBP, which triggers the loss of immune immunity of hair follicles and promotes the development of AA.

INFγ, interferon gamma; STAT, signal transducer and activator; P, phosphorylated; TCR, T cell receptor; NKG2D, NK cell receptor D; XO, xanthine oxidase; and iNOS, inducible nitric oxide synthase. IL also stimulates the proliferation and activation of T cells, macrophages, and CD5 memory lymphocytes.

They interact with each other to promote the progress of hair follicle inflammation. IFN-γ, IL-1β, and IL-6 are known as oxidative stress triggers. It has been shown that IFN-γ is a key player in xanthine oxidase XO -mediated oxidative stress. Light irradiation can induce an increase in XO activity in epidermal keratinocytes and endothelial cells and produce more oxygen free radicals In addition, XO and its oxidative stress products are also involved in the innate immunity of the skin.

XO appears in the early stage of skin inflammation caused by lipopolysaccharides LPS, a strong stimulator of toll-like receptors The activity of inducible nitric oxide synthase iNOS was also significantly increased in LPS-induced inflammatory skin disease mouse models.

iNOS are mainly found in fibroblasts, and a large amount of ·NO is synthesized in skin healing and skin inflammation caused by UV irradiation 40 , IFN-γ and IL-1β can induce the rapid expression of iNOS Figure 1 Tomaszewska et al.

However, there was no correlation between the levels of these three serum cytokines and disease degree SALT and disease activity VIDA Oxidative stress has been shown to upregulate NKG2D ligands, including MICA and ULBP, which may trigger the collapse of hair follicle immune privilege HF-IP and contribute to the development of alopecia areata 4.

Interestingly, studies have found that ULBP6 and ULBP3 are NKG2D ligands specifically associated with alopecia areata. More importantly, SNPs of antioxidant coding genes PRDX5 and ALDH2 have been identified as associated with the alopecia areata phenotype.

Some studies hypothesized that these two SNPs hypotheses may interfere with the hair growth cycle in affected individuals 46 , Recently, many studies have focused on the role of autophagy in AA.

Interfering with autophagy in AA may impair the clearance of dead cell debris; disrupt active hair growth in anagen, which leads to skin tissue inflammation Petukhova et al.

Simultaneously, autophagy plays a crucial role in antigen processing or presentation, which could reduce the expression of MHC class I molecules, which are abnormally downregulated in AA Gund et al.

Hardman et al. Autophagy protects cells from ROS by degrading and recycling damaged cellular components. In response to oxidative stress, ubiquitination of ATG9A a multi-spanning transmembrane protein induces autophagy Psychological stress, such as depression and anxiety, has been reported to be more common in patients with AA than in healthy individuals.

Their psychological state can be assessed by clinical psychiatric evaluation such as hospital anxiety scale score HADS-A score , and depression scale score HADS-D score , among others.

This is attributed to the shame and impaired self-esteem caused by hair loss, which can affect appearance 54 , Although it is still controversial whether depression and anxiety are pathogenic factors of AA, some studies suggest that patients who experienced acute psychological stress events for a long time mostly in childhood , such as academic pressure or death of close family members, may have a higher risk of developing AA.

The pathophysiological mechanism of hair loss induced by psychological stress may be associated with the upregulation of corticotropin-releasing hormone receptor CRHR , adrenocorticotropin ACTH , and acetylcholine ACh in the skin, which regulate immunity, promote cytokine secretion, and lead to the collapse of HF-IP 56 — Since both oxidative stress and psychological stress can trigger the collapse of HF-IP to cause alopecia areata, the relationship between these two factors needs to be explored.

Can depression, anxiety, or other mental states lead to further increase in oxidative stress levels in AA patients? A recent case—control study by Cakirca et al.

The study found that although total oxidation state TOS , total antioxidant capacity TAC , depression, and anxiety scores were significantly increased in AA patients compared to the control group, there was no significant difference between the scores and the TAS or the TOS levels of patients Hence, larger sample sizes, more extensive research, and more scientific evaluation criteria are needed to explore the interaction between psychological stress and oxidative stress.

The above studies not only indicate that oxidative stress may be one of the pathogenesis of alopecia areata, but also suggest that antioxidants can be used as an adjuvant therapy for alopecia areata, especially for patients with mild to moderate alopecia areata.

Currently, the treatments for alopecia areata mainly include glucocorticoids, contact immunotherapy, minoxidil, immunosuppressants, etc. Continued use of glucocorticoids may increase the chances of patients experiencing side effects, such as infections, ulcers, osteoporosis, and elevated blood sugar.

While the benefits of single antioxidant therapy may be limited and may even have negative effects, for example, long-term use of beta-carotene may increase the incidence of lung cancer in smokers 60 , while vitamin E may increase the risk of bleeding in people with oral anticoagulants and even reduce the lipid-lowering effect of statins 61 , Therefore, the safety and efficacy of long-term additional oral antioxidants deserve further exploration.

But in the case of alopecia areata, antioxidants as a form of combination therapy with steroids may help reduce steroid use. Calcipotriol is a vitamin D derivative.

Narang et al. Alam et al. However, studies such as double-blind clinical trials with larger samples are needed to further demonstrate the efficacy of vitamin D analogs in combination with other traditional therapies in patients with alopecia areata.