Top

Published in:

Open Access 22-09-2023 | Vitiligo | Review Article

Oxidative Stress and Potential Antioxidant Therapies in Vitiligo: A Narrative Review

Published in: Molecular Diagnosis & Therapy | Issue 6/2023

Abstract

Vitiligo is a chronic skin disorder characterised by the loss of melanocytes and subsequent skin depigmentation. Although many theories have been proposed in the literature, none alone explains the pathogenesis of vitiligo. Oxidative stress has been identified as a potential factor in the pathogenesis of vitiligo. A growing body of evidence suggests that antioxidant therapies may offer a promising approach to managing this condition. This review summarises the potential mechanisms of oxidative stress and the types of melanocyte death in vitiligo. We also provide a brief overview of the most commonly studied antioxidants. Melanocytes in vitiligo are thought to be damaged by an accumulation of reactive oxygen species to destroy the structural and functional integrity of their DNA, lipids, and proteins. Various causes, including exogenous and endogenous stress factors, an imbalance between prooxidants and antioxidants, disruption of antioxidant pathways, and gene polymorphisms, lead to the overproduction of reactive oxygen species. Although necroptosis, pyroptosis, ferroptosis, and oxeiptosis are newer types of cell death that may contribute to the pathophysiology of vitiligo, apoptosis remains the most studied cell death mechanism in vitiligo. According to studies, vitamin E helps to treat lipid peroxidation of the skin caused by psoralen ultra-violet A treatment. In addition, Polypodium leucotomos increased the efficacy of psoralen ultra-violet A or narrow-band ultraviolet B therapy. Our review provides valuable insights into the potential role of oxidative stress in pathogenesis and antioxidant-based supporting therapies in treating vitiligo, offering a promising avenue for further research and the development of effective treatment strategies.

Bergqvist C, Ezzedine K. Vitiligo: a review. Dermatol Basel Switz. 2020;236:571–92. https://doi.org/10.1159/000506103. CrossRef

Bergqvist C, Ezzedine K. Vitiligo: a focus on pathogenesis and its therapeutic implications. J Dermatol. 2021;48:252–70. https://doi.org/10.1111/1346-8138.15743. CrossRefPubMed

Czajkowski R, Placek W, Flisiak I, Krasowska D, Maj J, Marchlewicz M, et al. Vitiligo. Diagnostic and therapeutic recommendations of the Polish Dermatological Society. Dermatol Rev/Przegl Dermatol. 2019;106:1–15. https://doi.org/10.5114/dr.2019.83440. CrossRef

Zhang J, Hu W, Wang P, Ding Y, Wang H, Kang X. Research progress on targeted antioxidant therapy and vitiligo. Oxid Med Cell Longev. 2022;2022:1–10. https://doi.org/10.1155/2022/1821780. CrossRef

Lyu C, Sun Y. Immunometabolism in the pathogenesis of vitiligo. Front Immunol. 2022;13:1055958. https://doi.org/10.3389/fimmu.2022.1055958. CrossRefPubMedPubMedCentral

Kang P, Chen J, Zhang W, Guo N, Yi X, Cui T, et al. Oxeiptosis: a novel pathway of melanocytes death in response to oxidative stress in vitiligo. Cell Death Discov. 2022;8:70. https://doi.org/10.1038/s41420-022-00863-3. CrossRefPubMedPubMedCentral

Zhou Y, Khan M, Jiang L, Fu C, Dong Y, Luo L, et al. The current status of antioxidants in the treatment of vitiligo in China. Oxid Med Cell Longev. 2022;2022:2994558. https://doi.org/10.1155/2022/2994558. CrossRefPubMedPubMedCentral

Taieb A, Alomar A, Böhm M, Dell’Anna ML, De Pase A, Eleftheriadou V, et al. Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Br J Dermatol. 2013;168:5–19. https://doi.org/10.1111/j.1365-2133.2012.11197.x. CrossRefPubMed

Mulayim MK, Kurutas EB, Nazik H, Ozturk P. Assessment of oxidative/nitrosative stress and raftlin in vitiligo. Indian J Dermatol. 2022;67:624. https://doi.org/10.4103/ijd.ijd_917_20. CrossRefPubMedPubMedCentral

10.

Mitra S, De Sarkar S, Pradhan A, Pati AK, Pradhan R, Mondal D, et al. Levels of oxidative damage and proinflammatory cytokines are enhanced in patients with active vitiligo. Free Radic Res. 2017;51:986–94. https://doi.org/10.1080/10715762.2017.1402303. CrossRefPubMed

11.

Xie H, Zhou F, Liu L, Zhu G, Li Q, Li C, et al. Vitiligo: how do oxidative stress-induced autoantigens trigger autoimmunity? J Dermatol Sci. 2016;81:3–9. https://doi.org/10.1016/j.jdermsci.2015.09.003. CrossRefPubMed

12.

Chen J, Li S, Li C, Li CC. Mechanisms of melanocyte death in vitiligo. Med Res Rev. 2020;41:1138–66. https://doi.org/10.1002/med.21754. CrossRefPubMedPubMedCentral

13.

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. https://doi.org/10.1038/jid.2014.65. CrossRefPubMedPubMedCentral

14.

Lu Y, Tonissen KF, Di Trapani G. Modulating skin colour: role of the thioredoxin and glutathione systems in regulating melanogenesis. Biosci Rep. 2021;41:BSR20210427. https://doi.org/10.1042/BSR20210427. CrossRefPubMedPubMedCentral

15.

Mathachan SR, Khurana A, Gautam RK, Kulhari A, Sharma L, Sardana K. Does oxidative stress correlate with disease activity and severity in vitiligo? An analytical study. J Cosmet Dermatol. 2021;20:352–9. https://doi.org/10.1111/jocd.13499. CrossRefPubMed

16.

Said ER, Nagui NAER, Rashed LA, Mostafa WZ. Oxidative stress and the cholinergic system in non-segmental vitiligo: effect of narrow band ultraviolet b. Photodermatol Photoimmunol Photomed. 2021;37:306–12. https://doi.org/10.1111/phpp.12653. CrossRefPubMed

17.

Nie X-J, Hao B-Z, Zhang B-L, Li Y-Y. GATA3 ameliorates melanocyte injuries in vitiligo through SIRT3-mediated HMGB1 deacetylation. J Dermatol. 2023;50:472–84. https://doi.org/10.1111/1346-8138.16634. CrossRefPubMed

18.

Hu Y, Huang J, Li Y, Jiang L, Ouyang Y, Li Y, et al. Cistanche deserticola polysaccharide induces melanogenesis in melanocytes and reduces oxidative stress via activating NRF2/HO-1 pathway. J Cell Mol Med. 2020;24:4023–35. https://doi.org/10.1111/jcmm.15038. CrossRefPubMedPubMedCentral

19.

Zhou J, An X, Dong J, Wang Y, Zhong H, Duan L, et al. IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo. FASEB J. 2018;32:4899–916. https://doi.org/10.1096/fj.201701242RR. CrossRefPubMed

20.

He S, Xu J, Wu J. The promising role of chemokines in vitiligo: from oxidative stress to the autoimmune response. Oxid Med Cell Longev. 2022;2022:8796735. https://doi.org/10.1155/2022/8796735. CrossRefPubMedPubMedCentral

21.

Li S, Zhu G, Yang Y, Guo S, Dai W, Wang G, et al. Oxidative stress-induced chemokine production mediates CD8(+) T cell skin trafficking in vitiligo. J Investig Dermatol Symp Proc. 2015;17:32–3. https://doi.org/10.1038/jidsymp.2015.8. CrossRefPubMed

22.

Chen X, Guo W, Chang Y, Chen J, Kang P, Yi X, et al. Oxidative stress-induced IL-15 trans-presentation in keratinocytes contributes to CD8+ T cells activation via JAK-STAT pathway in vitiligo. Free Radic Biol Med. 2019;139:80–91. https://doi.org/10.1016/j.freeradbiomed.2019.05.011. CrossRefPubMed

23.

Li S, Zhu G, Yang Y, Jian Z, Guo S, Dai W, et al. Oxidative stress drives CD8+ T-cell skin trafficking in patients with vitiligo through CXCL16 upregulation by activating the unfolded protein response in keratinocytes. J Allergy Clin Immunol. 2017;140:177-89.e9. https://doi.org/10.1016/j.jaci.2016.10.013. CrossRefPubMed

24.

Ahn Y, Seo J, Lee EJ, Kim JY, Park M-Y, Hwang S, et al. ATP-P2X7-induced inflammasome activation contributes to melanocyte death and CD8+ T-cell trafficking to the skin in vitiligo. J Invest Dermatol. 2020;140:1794-804.e4. https://doi.org/10.1016/j.jid.2019.12.035. CrossRefPubMed

25.

Chang W-L, Ko C-H. The role of oxidative stress in vitiligo: an update on its pathogenesis and therapeutic implications. Cells. 2023;12:936. https://doi.org/10.3390/cells12060936. CrossRefPubMedPubMedCentral

26.

Xuan Y, Yang Y, Xiang L, Zhang C. The role of oxidative stress in the pathogenesis of vitiligo: a culprit for melanocyte death. Oxid Med Cell Longev. 2022;2022:8498472. https://doi.org/10.1155/2022/8498472. CrossRefPubMedPubMedCentral

27.

Jian Z, Li K, Liu L, Zhang Y, Zhou Z, Li C, et al. Heme oxygenase-1 protects human melanocytes from H ₂O ₂-induced oxidative stress via the Nrf2-ARE pathway. J Invest Dermatol. 2011;131:1420–7. https://doi.org/10.1038/jid.2011.56. CrossRefPubMed

28.

Białczyk A, Czajkowski R. Autophagy in psoriasis and vitiligo. Forum Dermatol. 2022;8:153–7. https://doi.org/10.5603/FD.a2022.0022. CrossRef

29.

He Y, Li S, Zhang W, Dai W, Cui T, Wang G, et al. Dysregulated autophagy increased melanocyte sensitivity to H ₂O ₂-induced oxidative stress in vitiligo. Sci Rep. 2017;7:42394. https://doi.org/10.1038/srep42394. CrossRefPubMedPubMedCentral

30.

Sorour NE, Abd El-Kareem HM, Ibrahim AE, Salem RM. Nuclear factor erythroid-2-related factor 2 gene polymorphisms in vitiligo. J Clin Aesthetic Dermatol. 2021;14:14–7.

31.

Ji Z, Liu G-H, Qu J. Mitochondrial sirtuins, metabolism, and aging. J Genet Genomics Yi Chuan Xue Bao. 2022;49:287–98. https://doi.org/10.1016/j.jgg.2021.11.005. CrossRefPubMed

32.

Yi X, Guo W, Shi Q, Yang Y, Zhang W, Chen X, et al. SIRT3-dependent mitochondrial dynamics remodeling contributes to oxidative stress-induced melanocyte degeneration in vitiligo. Theranostics. 2019;9:1614–33. https://doi.org/10.7150/thno.30398. CrossRefPubMedPubMedCentral

33.

Hayran Y, Özge Ergen G, Özmen F. The relationship between non-segmental Vitiligo, HLA genotype and oxidative stress. Int J Clin Pract. 2021;75: e14024. https://doi.org/10.1111/ijcp.14024. CrossRefPubMed

34.

Huang Y-W, Tsai T-F. HLA-Cw1 and psoriasis. Am J Clin Dermatol. 2021;22:339–47. https://doi.org/10.1007/s40257-020-00585-1. CrossRefPubMedPubMedCentral

35.

Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Res. 2019;29:347–64. https://doi.org/10.1038/s41422-019-0164-5. CrossRefPubMedPubMedCentral

36.

Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D, et al. Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ. 2015;22:58–73. https://doi.org/10.1038/cdd.2014.137. CrossRefPubMed

37.

Wu X, Yang Y, Xiang L, Zhang C. The fate of melanocyte: mechanisms of cell death in vitiligo. Pigment Cell Melanoma Res. 2021;34:256–67. https://doi.org/10.1111/pcmr.12955. CrossRefPubMed

38.

Sastry KS, Naeem H, Mokrab Y, Chouchane AI. RNA-seq reveals dysregulation of novel melanocyte genes upon oxidative stress: implications in vitiligo pathogenesis. Oxid Med Cell Longev. 2019;2019:2841814. https://doi.org/10.1155/2019/2841814. CrossRefPubMedPubMedCentral

39.

D’Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 2019;43:582–92. https://doi.org/10.1002/cbin.11137. CrossRefPubMed

40.

Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495–516. https://doi.org/10.1080/01926230701320337. CrossRefPubMedPubMedCentral

41.

Campioni M, Santini D, Tonini G, Murace R, Dragonetti E, Spugnini EP, et al. Role of Apaf-1, a key regulator of apoptosis, in melanoma progression and chemoresistance. Exp Dermatol. 2005;14:811–8. https://doi.org/10.1111/j.1600-0625.2005.00360.x. CrossRefPubMed

42.

McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2013;5: a008656. https://doi.org/10.1101/cshperspect.a008656. CrossRefPubMedPubMedCentral

43.

Raisova M, Hossini AM, Eberle J, Riebeling C, Wieder T, Sturm I, et al. The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. J Invest Dermatol. 2001;117:333–40. https://doi.org/10.1046/j.0022-202x.2001.01409.x. CrossRefPubMed

44.

Kumar R, Parsad D, Kanwar AJ, Kaul D. Altered levels of LXR-α: crucial implications in the pathogenesis of vitiligo. Exp Dermatol. 2012;21:853–8. https://doi.org/10.1111/exd.12017. CrossRefPubMed

45.

Park K, Lee SE, Shin K-O, Uchida Y. Insights into the role of endoplasmic reticulum stress in skin function and associated diseases. FEBS J. 2019;286:413–25. https://doi.org/10.1111/febs.14739. CrossRefPubMedPubMedCentral

46.

Liu X, Hussain R, Mehmood K, Tang Z, Zhang H, Li Y. Mitochondrial-endoplasmic reticulum communication-mediated oxidative stress and autophagy. BioMed Res Int. 2022;2022:6459585. https://doi.org/10.1155/2022/6459585. CrossRefPubMedPubMedCentral

47.

Chen J, Zhuang T, Chen J, Tian Y, Yi X, Ni Q, et al. Homocysteine induces melanocytes apoptosis via PERK-eIF2α-CHOP pathway in vitiligo. Clin Sci Lond. 2020;134:1127–41. https://doi.org/10.1042/CS20200218. CrossRefPubMed

48.

Lossi L. The concept of intrinsic versus extrinsic apoptosis. Biochem J. 2022;479:357–84. https://doi.org/10.1042/BCJ20210854. CrossRefPubMed

49.

Jimbo H, Nagai H, Fujiwara S, Shimoura N, Nishigori C. Fas-FasL interaction in cytotoxic T cell-mediated vitiligo: the role of lesional expression of tumor necrosis factor-α and interferon-γ in Fas-mediated melanocyte apoptosis. Exp Dermatol. 2020;29:61–70. https://doi.org/10.1111/exd.14053. CrossRefPubMed

50.

Tulic MK, Cavazza E, Cheli Y, Jacquel A, Luci C, Cardot-Leccia N, et al. Innate lymphocyte-induced CXCR3B-mediated melanocyte apoptosis is a potential initiator of T-cell autoreactivity in vitiligo. Nat Commun. 2019;10:2178. https://doi.org/10.1038/s41467-019-09963-8. CrossRefPubMedPubMedCentral

51.

Shi Q, Zhang W, Guo S, Jian Z, Li S, Li K, et al. Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo. Cell Death Differ. 2016;23:496–508. https://doi.org/10.1038/cdd.2015.117. CrossRefPubMed

52.

Mou K, Liu W, Miao Y, Cao F, Li P. HMGB1 deficiency reduces H ₂O ₂-induced oxidative damage in human melanocytes via the Nrf2 pathway. J Cell Mol Med. 2018;22:6148–56. https://doi.org/10.1111/jcmm.13895. CrossRefPubMedPubMedCentral

53.

Kim JY, Lee EJ, Seo J, Oh SH. Impact of high-mobility group box 1 on melanocytic survival and its involvement in the pathogenesis of vitiligo. Br J Dermatol. 2017;176:1558–68. https://doi.org/10.1111/bjd.15151. CrossRefPubMed

54.

Jorgensen I, Miao EA. Pyroptotic cell death defends against intracellular pathogens. Immunol Rev. 2015;265:130–42. https://doi.org/10.1111/imr.12287. CrossRefPubMedPubMedCentral

55.

Shi J, Gao W, Shao F. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci. 2017;42:245–54. https://doi.org/10.1016/j.tibs.2016.10.004. CrossRefPubMed

56.

Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016;535:153–8. https://doi.org/10.1038/nature18629. CrossRefPubMedPubMedCentral

57.

Faria SS, Costantini S, de Lima VCC, de Andrade VP, Rialland M, Cedric R, et al. NLRP3 inflammasome-mediated cytokine production and pyroptosis cell death in breast cancer. J Biomed Sci. 2021;28:26. https://doi.org/10.1186/s12929-021-00724-8. CrossRefPubMedPubMedCentral

58.

Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci. 2019;20:3328. https://doi.org/10.3390/ijms20133328. CrossRefPubMedPubMedCentral

59.

Marie J, Kovacs D, Pain C, Jouary T, Cota C, Vergier B, et al. Inflammasome activation and vitiligo/nonsegmental vitiligo progression. Br J Dermatol. 2014;170:816–23. https://doi.org/10.1111/bjd.12691. CrossRefPubMed

60.

Zhou Z, He H, Wang K, Shi X, Wang Y, Su Y, et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science. 2020;368: eaaz7548. https://doi.org/10.1126/science.aaz7548. CrossRefPubMed

61.

Nirmala JG, Lopus M. Cell death mechanisms in eukaryotes. Cell Biol Toxicol. 2020;36:145–64. https://doi.org/10.1007/s10565-019-09496-2. CrossRefPubMed

62.

Mozaffari S, Abdollahi M. Chapter 3. Mitochondrial contribution to cell death. In: Pourahmad J, Rezaei M, editors. Mitochondrial metabolism. New York: Academic Press; 2021. p. 49–60. https://doi.org/10.1016/B978-0-12-822416-8.00004-X. CrossRef

63.

Chaouhan HS, Vinod C, Mahapatra N, Yu S-H, Wang I-K, Chen K-B, et al. Necroptosis: a pathogenic negotiator in human diseases. Int J Mol Sci. 2022;23:12714. https://doi.org/10.3390/ijms232112714. CrossRefPubMedPubMedCentral

64.

Zhang Y, Su SS, Zhao S, Yang Z, Zhong C-Q, Chen X, et al. RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat Commun. 2017;8:14329. https://doi.org/10.1038/ncomms14329. CrossRefPubMedPubMedCentral

65.

Li B, Yi X, Zhuang T, Zhang S, Li S, Yang Y, et al. RIP1-mediated necroptosis facilitates oxidative stress-induced melanocyte death, offering insight into vitiligo. J Invest Dermatol. 2021;141:2921-31.e6. https://doi.org/10.1016/j.jid.2020.06.042. CrossRefPubMed

66.

Li J, Cao F, Yin H, Huang Z, Lin Z, Mao N, et al. Ferroptosis: past, present and future. Cell Death Dis. 2020;11:88. https://doi.org/10.1038/s41419-020-2298-2. CrossRefPubMedPubMedCentral

67.

Jiang X, Stockwell BR, Conrad M. Ferroptosis: mechanisms, biology, and role in disease. Nat Rev Mol Cell Biol. 2021;22:266. https://doi.org/10.1038/S41580-020-00324-8. CrossRefPubMedPubMedCentral

68.

Chen X, Kang R, Kroemer G, Tang D. Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol. 2021;18:280–96. https://doi.org/10.1038/s41571-020-00462-0. CrossRefPubMed

69.

Liu P, Wang W, Li Z, Li Y, Yu X, Tu J, et al. Ferroptosis: a new regulatory mechanism in osteoporosis. Oxid Med Cell Longev. 2022;2022:2634431. https://doi.org/10.1155/2022/2634431. CrossRefPubMedPubMedCentral

70.

Wang J, Liu Y, Wang Y, Sun L. The cross-link between ferroptosis and kidney diseases. Oxid Med Cell Longev. 2021;2021: e6654887. https://doi.org/10.1155/2021/6654887. CrossRef

71.

Yu Y, Yan Y, Niu F, Wang Y, Chen X, Su G, et al. Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases. Cell Death Discov. 2021;7:193. https://doi.org/10.1038/s41420-021-00579-w. CrossRefPubMedPubMedCentral

72.

Xuan Y, Yang Y, Xiang L, Zhang C. The role of oxidative stress in the pathogenesis of vitiligo: a culprit for melanocyte death. Oxid Med Cell Longev. 2022;2022: 849847. https://doi.org/10.1155/2022/8498472. CrossRef

73.

Zhao Y, Li Y, Zhang R, Wang F, Wang T, Jiao Y. The role of erastin in ferroptosis and its prospects in cancer therapy. Onco Targets Ther. 2020;13:5429–41. https://doi.org/10.2147/OTT.S254995. CrossRefPubMedPubMedCentral

74.

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060–72. https://doi.org/10.1016/j.cell.2012.03.042. CrossRefPubMedPubMedCentral

75.

Xiao B-H, Shi M, Chen H, Cui S, Wu Y, Gao X-H, et al. Glutathione peroxidase level in patients with vitiligo: a meta-analysis. BioMed Res Int. 2016;2016:3029810. https://doi.org/10.1155/2016/3029810. CrossRefPubMedPubMedCentral

76.

Yang M, Li X, Li H, Zhang X, Liu X, Song Y. Baicalein inhibits RLS3-induced ferroptosis in melanocytes. Biochem Biophys Res Commun. 2021;561:65–72. https://doi.org/10.1016/J.BBRC.2021.05.010. CrossRefPubMed

77.

Wu X, Jin S, Yang Y, Lu X, Dai X, Xu Z, et al. Altered expression of ferroptosis markers and iron metabolism reveals a potential role of ferroptosis in vitiligo. Pigment Cell Melanoma Res. 2022;35:328–41. https://doi.org/10.1111/pcmr.13032. CrossRefPubMed

78.

Holze C, Michaudel C, Mackowiak C, Haas DA, Benda C, Hubel P, et al. Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway. Nat Immunol. 2018;19:130–40. https://doi.org/10.1038/s41590-017-0013-y. CrossRefPubMed

79.

Tian C, Liu Y, Li Z, Zhu P, Zhao M. Mitochondria related cell death modalities and disease. Front Cell Dev Biol. 2022;10: 832356. https://doi.org/10.3389/fcell.2022.832356. CrossRefPubMed

80.

Michalak M. Plant-derived antioxidants: significance in skin health and the ageing process. Int J Mol Sci. 2022;23:585. https://doi.org/10.3390/ijms23020585. CrossRefPubMedPubMedCentral

81.

Pai VV, Shukla P, Kikkeri NN. Antioxidants in dermatology. Indian Dermatol Online J. 2014;5:210. https://doi.org/10.4103/2229-5178.131127. CrossRefPubMedPubMedCentral

82.

Jung YY, Ha IJ, Lee M, Ahn KS. Skin improvement with antioxidant effect of Yuja ( Citrus junos) peel fractions: wrinkles, moisturizing, and whitening. Antioxidants (Basel). 2022;12:51. https://doi.org/10.3390/antiox12010051. CrossRefPubMedPubMedCentral

83.

Masaki H. Role of antioxidants in the skin: anti-aging effects. J Dermatol Sci. 2010;58:85–90. https://doi.org/10.1016/j.jdermsci.2010.03.003. CrossRefPubMed

84.

Sable KA, Shields BE. The role of dietary antioxidants in melanoma and nonmelanoma skin cancer. Cutis. 2023;111:33–48. https://doi.org/10.12788/cutis.0672. CrossRefPubMed

85.

Guarneri F, Bertino L, Pioggia G, Casciaro M, Gangemi S. Therapies with antioxidant potential in psoriasis, vitiligo, and lichen planus. Antioxidants. 2021;10:1087. https://doi.org/10.3390/antiox10071087. CrossRefPubMedPubMedCentral

86.

Xing X, Dan Y, Xu Z, Xiang L. Implications of oxidative stress in the pathogenesis and treatment of hyperpigmentation disorders. Oxid Med Cell Longev. 2022;2022:7881717. https://doi.org/10.1155/2022/7881717. CrossRefPubMedPubMedCentral

87.

Khan R, Satyam A, Gupta S, Sharma VK, Sharma A. Circulatory levels of antioxidants and lipid peroxidation in Indian patients with generalized and localized vitiligo. Arch Dermatol Res. 2009;301:731–7. https://doi.org/10.1007/s00403-009-0964-4. CrossRefPubMed

88.

Sendrasoa FA, Ranaivo IM, Sata M, Andrianarison M, Raharolahy O, Rakotoarisaona MF, et al. Treatment responses in patients with vitiligo to very potent topical corticosteroids combined with vitaminotherapy in Madagascar. Int J Dermatol. 2019;58:908–11. https://doi.org/10.1111/ijd.14510. CrossRefPubMed

89.

Sardana K, Sachdeva S. Role of nutritional supplements in selected dermatological disorders: a review. J Cosmet Dermatol. 2022;21:85–98. https://doi.org/10.1111/JOCD.14436. CrossRefPubMed

90.

Liu X, Yang G, Luo M, Lan Q, Shi X, Deng H, et al. Serum vitamin E levels and chronic inflammatory skin diseases: a systematic review and meta-analysis. PLoS ONE. 2021;16: e0261259. https://doi.org/10.1371/JOURNAL.PONE.0261259. CrossRefPubMedPubMedCentral

91.

Akyol M, Celik VK, Ozcelik S, Polat M, Marufihah M, Atalay A. The effects of vitamin E on the skin lipid peroxidation and the clinical improvement in vitiligo patients treated with PUVA. Eur J Dermatol. 2002;12:24–6. PubMed

92.

Elgoweini M, Din NNE. Response of vitiligo to narrowband ultraviolet B and oral antioxidants. J Clin Pharmacol/. 2009;49:852–5. https://doi.org/10.1177/0091270009335769. CrossRefPubMed

93.

Dell’Anna ML, Mastrofrancesco A, Sala R, Venturini M, Ottaviani M, Vidolin AP, et al. Antioxidants and narrow band-UVB in the treatment of vitiligo: a double-blind placebo controlled trial. Clin Exp Dermatol. 2007;32:631–6. https://doi.org/10.1111/J.1365-2230.2007.02514.X. CrossRefPubMed

94.

Nowowiejska L, Marek-Józefowicz L, Szewczyk-Golec K, Woźniak A, Basałygo M, Zegarska B, et al. Influence of oral supplementation of vitamins A and E on the effectiveness of vitiligo treatment. Dermatol Ther. 2023;2023:1–7. https://doi.org/10.1155/2023/3777109. CrossRef

95.

Dai T, Xiaoying S, Li X, Hongjin L, Yaqiong Z, Bo L. Selenium level in patients with vitiligo: a meta-analysis. BioMed Res Int. 2020;2020:7580939. https://doi.org/10.1155/2020/7580939. CrossRefPubMedPubMedCentral

96.

Lv J, Ai P, Lei S, Zhou F, Chen S, Zhang Y. Selenium levels and skin diseases: systematic review and meta-analysis. J Trace Elem Med Biol. 2020;62: 126548. https://doi.org/10.1016/j.jtemb.2020.126548. CrossRefPubMed

97.

Huo J, Liu T, Huan Y, Li F, Wang R. Serum level of antioxidant vitamins and minerals in patients with vitiligo, a systematic review and meta-analysis. J Trace Elem Med Biol. 2020;62: 126570. https://doi.org/10.1016/j.jtemb.2020.126570. CrossRefPubMed

98.

Sanad EM, El-Fallah AA, Al-Doori AR, Salem RM. Serum zinc and inflammatory cytokines in vitiligo. J Clin Aesthetic Dermatol. 2020;13:S29.

99.

Zaki AM, Nada AS, Elshahed AR, Abdelgawad NH, Jafferany M, Elsaie ML. Therapeutic implications of assessment of serum zinc levels in patients with vitiligo: a patient controlled prospective study. Dermatol Ther. 2020;33: e13998. https://doi.org/10.1111/dth.13998. CrossRefPubMed

100.

Bagherani N, Yaghoobi R, Omidian M. Hypothesis: zinc can be effective in treatment of vitiligo. Indian J Dermatol. 2011;56:480–4. https://doi.org/10.4103/0019-5154.87116. CrossRefPubMedPubMedCentral

101.

Osredkar J. Copper and zinc, biological role and significance of copper/zinc imbalance. J Clin Toxicol. 2011;S3:001. https://doi.org/10.4172/2161-0495.S3-001. CrossRef

102.

Wacewicz M, Socha K, Soroczyńska J, Niczyporuk M, Aleksiejczuk P, Ostrowska J, et al. Selenium, zinc, copper, Cu/Zn ratio and total antioxidant status in the serum of vitiligo patients treated by narrow-band ultraviolet-B phototherapy. J Dermatol Treat. 2018;29:190–5. https://doi.org/10.1080/09546634.2017.1357797. CrossRef

103.

Zeng Q, Yin J, Fan F, Chen J, Zuo C, Xiang Y, et al. Decreased copper and zinc in sera of Chinese vitiligo patients: a meta-analysis. J Dermatol. 2014;41:245–51. https://doi.org/10.1111/1346-8138.12392. CrossRefPubMed

104.

Khoshdel Z, Gholijani N, Niknam M, Rahmani N, Hemmati-Dinarvand M, Naghibalhossaini F. Serum copper and zinc levels among Iranian vitiligo patients. Dermatol Pract Concept. 2022;12: e2022140. https://doi.org/10.5826/dpc.1204a140. CrossRefPubMedPubMedCentral

105.

Narang I, Deb Barman K, Sahoo B, Lali P. Evaluation of serum levels of zinc and copper in vitiligo. Pigment Int. 2021;8:42–7. https://doi.org/10.4103/Pigmentinternational.Pigmentinternational. CrossRef

106.

Lu L, Wang S, Fu L, Liu D, Zhu Y, Xu A. Bilobalide protection of normal human melanocytes from hydrogen peroxide-induced oxidative damage via promotion of antioxidase expression and inhibition of endoplasmic reticulum stress. Clin Exp Dermatol. 2016;41:64–73. https://doi.org/10.1111/ced.12664. CrossRefPubMed

107.

Zhang S, Yi X, Su X, Jian Z, Cui T, Guo S, et al. Ginkgo biloba extract protects human melanocytes from H ₂O ₂-induced oxidative stress by activating Nrf2. J Cell Mol Med. 2019;23:5193–9. https://doi.org/10.1111/jcmm.14393. CrossRefPubMedPubMedCentral

108.

Parsad D, Pandhi R, Juneja A. Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo. Clin Exp Dermatol. 2003;28:285–7. CrossRefPubMed

109.

Szczurko O, Shear N, Taddio A, Boon H. Ginkgo biloba for the treatment of vitiligo vulgaris: an open label pilot clinical trial. BMC Complement Altern Med. 2011;15:21. https://doi.org/10.1186/1472-6882-11-21. CrossRef

110.

Jamgochian M, Alamgir M, Rao B. Diet in dermatology: review of diet’s influence on the conditions of rosacea, hidradenitis suppurativa, herpes labialis, and vitiligo. Am J Lifestyle Med. 2021;17:152–60. https://doi.org/10.1177/15598276211026592. CrossRefPubMedPubMedCentral

111.

Mahomoodally MF, Désiré A-LD, Rosette MA-LE. Catalase. In: Nabavi SM, Silva AS, editors. Antioxidants effects in health. Amsterdam: Elsevier; 2022. p. 81–90. https://doi.org/10.1016/B978-0-12-819096-8.00022-7. CrossRef

112.

Sravani PV, Babu NK, Gopal KVT, Rao GRR, 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. https://doi.org/10.4103/0378-6323.48427. CrossRefPubMed

113.

Li S, Dai W, Wang S, Kang P, Ye Z, Han P, et al. Clinical significance of serum oxidative stress markers to assess disease activity and severity in patients with non-segmental vitiligo. Front Cell Dev Biol. 2021;9: 739413. https://doi.org/10.3389/fcell.2021.739413. CrossRefPubMedPubMedCentral

114.

Ines D, Sonia B, Riadh BM, Amel EG, Slaheddine M, Hamida T, et al. A comparative study of oxidant-antioxidant status in stable and active vitiligo patients. Arch Dermatol Res. 2006;298:147–52. https://doi.org/10.1007/s00403-006-0680-2. CrossRefPubMed

115.

Hazneci E, Karabulut AB, Ozturk C, Batcioglu K, Dogan 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. https://doi.org/10.1111/j.1365-4632.2004.02027.x. CrossRefPubMed

116.

Naini FF, Shooshtari AV, Ebrahimi B, Molaei R. The effect of pseudocatalase/superoxide dismutase in the treatment of vitiligo: a pilot study. J Res Pharm Pract. 2012;1:77–80. https://doi.org/10.4103/2279-042X.108375. CrossRefPubMedPubMedCentral

117.

Alshiyab DM, Al-Qarqaz FA, Muhaidat JM, Alkhader YS, Al-Sheyab RF, Jafaar SI. Comparison of the efficacy of tacrolimus 0.1% ointment and tacrolimus 0.1% plus topical pseudocatalase/superoxide dismutase gel in children with limited vitiligo: a randomized controlled trial. J Dermatol Treat. 2022;33:146–9. https://doi.org/10.1080/09546634.2020.1729952. CrossRef

118.

Bakis-Petsoglou S, Le Guay JL, Wittal R. A randomized, double-blinded, placebo-controlled trial of pseudocatalase cream and narrowband ultraviolet B in the treatment of vitiligo. Br J Dermatol. 2009;161:910–7. https://doi.org/10.1111/j.1365-2133.2009.09252.x. CrossRefPubMed

119.

Patel DC, Evans AV, Hawk JLM. Topical pseudocatalase mousse and narrowband UVB phototherapy is not effective for vitiligo: an open, single-centre study. Clin Exp Dermatol. 2002;27:641–4. https://doi.org/10.1046/J.1365-2230.2002.01142.X. CrossRefPubMed

120.

Schallreuter KU, Wood JM, Lemke KR, Levenig C. Treatment of vitiligo with a topical application of pseudocatalase and calcium in combination with short-term UVB exposure: a case study on 33 patients. Dermatology. 1995;190:223–9. https://doi.org/10.1159/000246690. CrossRefPubMed

121.

Schallreuter KU, Krüger C, Würfel BA, Panske A, Wood JM. From basic research to the bedside: efficacy of topical treatment with pseudocatalase PC-KUS in 71 children with vitiligo. Int J Dermatol. 2008;47:743–53. https://doi.org/10.1111/j.1365-4632.2008.03660.x. CrossRefPubMed

122.

Schallreuter KU, Moore J, Behrens-Williams S, Panske A, Harari M. Rapid initiation of repigmentation in vitiligo with Dead Sea climatotherapy in combination with pseudocatalase (PC-KUS). Int J Dermatol. 2002;41:482–7. https://doi.org/10.1046/J.1365-4362.2002.01463.X. CrossRefPubMed

123.

Shi M-H, Wu Y, Li L, Cai Y-F, Liu M, Gao X-H, et al. Meta-analysis of the association between vitiligo and the level of superoxide dismutase or malondialdehyde. Clin Exp Dermatol. 2017;42:21–9. https://doi.org/10.1111/ced.12950. CrossRefPubMed

124.

Shakhbazova A, Wu H, Chambers CJ, Sivamani RK. A systematic review of nutrition, supplement, and herbal-based adjunctive therapies for vitiligo. J Altern Complement Med. 2021;27:294–311. https://doi.org/10.1089/acm.2020.0292. CrossRefPubMed

125.

Tóth F, Cseh EK, Vécsei L. Natural molecules and neuroprotection: kynurenic acid, pantethine and α-lipoic acid. Int J Mol Sci. 2021;22:403. https://doi.org/10.3390/ijms22010403. CrossRefPubMedPubMedCentral

126.

Li L, Li L, Wu Y, Gao XH, Chen HD. Triple-combination treatment with oral α-lipoic acid, betamethasone injection, and NB-UVB for non-segmental progressive vitiligo. J Cosmet Laser Ther. 2016;18:182–5. https://doi.org/10.3109/14764172.2015.1114646. CrossRefPubMed

127.

Sun Y, Guan X, Wang H, Zhang J, Gu H, Lu H, et al. Randomized clinical trial of combined therapy with oral α-lipoic acid and NB-UVB for nonsegmental stable vitiligo. Dermatol Ther. 2021;34: e14610. https://doi.org/10.1111/dth.14610. CrossRefPubMed

128.

Hargreaves I, Heaton RA, Mantle D. Molecular sciences disorders of human coenzyme Q10 metabolism: an overview. Int J Mol Sci. 2020;21:6695. https://doi.org/10.3390/ijms21186695. CrossRefPubMedPubMedCentral

129.

Schallreuter KU. Q10-triggered facial vitiligo. Br J Dermatol. 2013;169:1333–6. https://doi.org/10.1111/bjd.12587. CrossRefPubMed

130.

Hameed MF, Abu-Raghif AR, Farhood IG, Ali NM. The effectiveness of systemic co-enzyme Q10 in vitiligo. Iraqi J Med Sci. 2013;11:67–71.

131.

Li Y, Sun HY, Yu XY, Liu D, Wan HX. Evaluation of cellular antioxidant and antiproliferative activities of five main Phyllanthus emblica L. cultivars in China. Indian J Pharm Sci. 2015;77:274. https://doi.org/10.4103/0250-474X.159608. CrossRefPubMedPubMedCentral

132.

Di Nardo V, Barygina V, França K, Tirant M, Valle Y, Lotti T. Functional nutrition as integrated approach in vitiligo management. Dermatol Ther. 2019;32: e12625. https://doi.org/10.1111/dth.12625. CrossRefPubMed

133.

Colucci R, Dragoni F, Conti R, Pisaneschi L, Lazzeri L, Moretti S. Evaluation of an oral supplement containing Phyllanthus emblica fruit extracts, vitamin E, and carotenoids in vitiligo treatment. Dermatol Ther. 2015;28:17–21. https://doi.org/10.1111/dth.12172. CrossRefPubMed

134.

Thompson KG, Kim N. Dietary supplements in dermatology: a review of the evidence for zinc, biotin, vitamin D, nicotinamide, and Polypodium. J Am Acad Dermatol. 2021;84:1042–50. https://doi.org/10.1016/j.jaad.2020.04.123. CrossRefPubMed

135.

Calzari P, Vaienti S, Nazzaro G. Uses of Polypodium leucotomos extract in oncodermatology. J Clin Med. 2023;12:673. https://doi.org/10.3390/jcm12020673. CrossRefPubMedPubMedCentral

136.

Middelkamp-Hup MA, Bos JD, Rius-diaz F, Gonzalez S, Westerhof W. Treatment of vitiligo vulgaris with narrow-band UVB and oral Polypodium leucotomos extract: a randomized double-blind placebo-controlled study. J Eur Acad Dermatol Venereol. 2007;21:942–50. https://doi.org/10.1111/J.1468-3083.2006.02132.X. CrossRefPubMed

137.

Reyes E, Jaén P, Heras EDL, Eusebio ED, Carrión F, Cuevas J, et al. Systemic immunomodulatory effects of Polypodium leucotomos as an adjuvant to PUVA therapy in generalized vitiligo: a pilot study. J Dermatol Sci. 2006;41:213–6. https://doi.org/10.1016/J.JDERMSCI.2005.12.006. CrossRefPubMed

138.

Pacifico A, Damiani G, Iacovelli P, Conic RRZ, Gonzalez S, Morrone A. NB-UVB plus oral Polypodium leucotomos extract display higher efficacy than NB-UVB alone in patients with vitiligo. Dermatol Ther. 2021;34: e14776. https://doi.org/10.1111/dth.14776. CrossRefPubMed

Title: Oxidative Stress and Potential Antioxidant Therapies in Vitiligo: A Narrative Review
Publication date: 22-09-2023
Keyword: Vitiligo
Published in: Molecular Diagnosis & Therapy / Issue 6/2023
Print ISSN: 1177-1062
Electronic ISSN: 1179-2000
DOI: https://doi.org/10.1007/s40291-023-00672-z

Webinar | 08-11-2023 | 18:00 (CET)

Keynote Webinar | Spotlight on Diet and Diabetes

Watch now

An expert-led symposium exploring the prevention and management of type 2 diabetes through dietary interventions. Highlights include discussion of the recent EASD guidelines, therapeutic diets, food types and processing, plus psychological factors that influence patient success, and the drivers of healthy eating and diabetes control.

Prof. Mike Lean

Prof. Falko Sniehotta

Keynote Webinar | Spotlight on Diet and Diabetes

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2023

Clinical Potential of Expanded Noninvasive Prenatal Testing for Detection of Aneuploidies and Microdeletion/Microduplication Syndromes

MicroRNAs Function in Dental Stem Cells as a Promising Biomarker and Therapeutic Target for Dental Diseases

Preliminary Study of Whole-Genome Bisulfite Sequencing and Transcriptome Sequencing in VHL Disease-Associated ccRCC

Steps to Improve Precision Medicine in Epilepsy

Optimizing CAR-T Therapy for Glioblastoma

Equecabtagene Autoleucel: First Approval

Keynote Webinar | Spotlight on Diet and Diabetes