Aktif ve Generalize Vitiligolu Hastalarda Azalmış Oksidatif Stres Belirteçleri

Yıl 2022, Cilt: 14 Sayı: 2, 317 - 322, 29.06.2022

Yunus Ozcan Ebru Karagün Merve Alpay

https://doi.org/10.18521/ktd.880577

Öz

Amaç
Oksidatif stresin, birçok hastalığın patofizyolojisinde rol oynadığı gösterilmiş ve bu da onu popüler ancak tartışmalı bir araştırma alanı haline getirmiştir. Vitiligo hastalarında, artmış oksidatif stres sonucu seçici melanosit hasarının gelişmiş olabileceği yönünde bazı kanıtlar vardır. Bu çalışmanın amacı, vitiligo hastalarında oksidatif stresin lipid, protein ve nükleik asit metabolizması üzerindeki etkisini araştırmaktır.
Metod
Son üç ayda yeni oluşan lezyonları olan ancak tedavi edilmemiş generalize vitiligolu hastalarda ve sağlıklı kontrollerde, serum oksidatif stres belirteçlerini ölçmek için ELISA metodunu kullandık. Reaktif oksijen türevlerinin lipid, protein, nükleik asit metabolizması ve mitokondri üzerindeki etkisini incelemek için sırasıyla malondialdehit (MDA), 2,4-dinitrofenil hidrazon (DNPH), 8-hidroksi-2'-deoksiguanozin (8-OHdG) ve ayırıcı protein 2 (UCP2) seviyeleri ölçüldü.
Bulgular
Çalışmaya 64 aktif generalize vitiligo hastası ve benzer yaş ve cinsiyet dağılımına sahip 20 sağlıklı kontrol olmak üzere toplam 84 katılımcı dahil edildi. Vitiligo hastalarının serumunda sağlıklı kontrollere göre anlamlı olarak azalmış MDA (ng/mL, ortalama±SS=12±19; 33.4±35.9), DNPH (ng/mL, ortalama±SS=2±3.1; 6±7.4), 8-OHdG (ng/mL, ortalama±SS=11.7±17.9; 32.7±37) ve UCP2 (ng/mL, ortalama±SS=8.7±13.7; 21.5±28.4) seviyeleri tespit edildi.
Sonuç
Oksidatif stresin vitiligo patofizyolojisinde rol oynadığına dair önemli kanıtlar olmasına rağmen, metodolojideki heterojenlik, oksidatif stres yolaklarının karmaşıklığı ve olası yayın yanlılığı açısından çalışmalar dikkatli bir şekilde yorumlanmalıdır. Vitiligonun merkezi patofizyolojisinde oksidatif stresin ne kadar önemli olduğunu ve öncelikle hangi yolakları etkilediğini belirlemek için standart bir metodoloji kullanan büyük ölçekli çalışmalar gereklidir.

Anahtar Kelimeler

Deoksiguanozin, malondialdehit, ayırıcı protein 2, vitiligo

Decreased Oxidative Stress Markers in Patients with Active and Generalized Vitiligo

Öz

Objective
Oxidative stress has been shown to play a role in the pathophysiology of several diseases, making it a popular yet contentious research area. There is some evidence that selective melanocyte destruction may have developed in vitiligo patients as a result of elevated oxidative stress. The purpose of this study is to investigate the impact of oxidative stress on lipid, protein, and nucleic acid metabolism in vitiligo patients.
Method
We used ELISA method to measure serum oxidative stress markers in patients with generalized vitiligo who had newly formed lesions in the previous three months but had not been treated, as well as healthy controls. Malondialdehyde (MDA), 2,4-dinitrophenyl hydrazone (DNPH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and uncoupling protein 2 (UCP2) levels were measured to assess the influence of reactive oxygen derivatives on lipid, protein, nucleic acid metabolism, and mitochondria, respectively.
Results
The study included 84 participants, including 64 active generalized vitiligo patients and 20 healthy controls with similar age and gender distribution. In the serum of vitiligo patients, we detected significantly lower levels of MDA (ng/mL, mean±SD=12±19; 33.4±35.9), DNPH (ng/mL, mean±SD=2±3.1; 6±7.4), 8-OHdG (ng/mL, mean±SD=11.7±17.9; 32.7±37) and UCP2 (ng/mL, mean±SD=8.7±13.7; 21.5±28.4).

Conclusion
Although there is significant evidence that oxidative stress plays a role in the pathophysiology of vitiligo, the studies should be interpreted cautiously due to the heterogeneity in the methodology, complexity of the oxidative stress pathways, and potential publication bias. Large-scale studies using a standardized methodology are required to determine how significant oxidative stress is in the core pathophysiology of vitiligo and which pathways it primarily affects.

Anahtar Kelimeler

oxidative stress, vitiligo, MDA, DNP, UCP-2, 8-OHDG

Kaynakça

• 1. Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE. New discoveries in the pathogenesis and classification of vitiligo. J Am Acad Dermatol. 2017;77:1-13. doi: https://doi.org/10.1016/j.jaad.2016.10.048.
• 2. Sushama S, Dixit N, Gautam RK, Arora P, Khurana A, Anubhuti A. Cytokine profile (IL-2, IL-6, IL-17, IL-22, and TNF-α) in vitiligo-New insight into pathogenesis of disease. J Cosmet Dermatol. 2019;18:337-41. https://doi.org/10.1111/jocd.12517.
• 3. Ines D, Sonia B, Riadh BM, Amel el G, 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
• 4. Arun KM, Sandhya M, Imran K, Govind R. Evaluation of oxidative stress and lipid profile in patients of generalized vitiligo. International Journal of Medical Science and Public Health. 2006;5:493-6. https://doi.org/10.5455/ijmsph. 2016.1008201590
• 5. Shi MH, Wu Y, Li L, Cai YF, Liu M, Gao XH, et al. Meta-analysis of the association between vitiligo and the level of superoxide dismutase or malondialdehyde. Clin Exp Dermatol. 2017;42:21-29. https://doi.org/10.1111/ced.12950.
• 6. Ho AW, Kupper TS. T cells and the skin: from protective immunity to inflammatory skin disorders. Nat Rev Immunol. 2019:19.490-502 https://doi.org/ 10.1038/s41577-019-0162-3.
• 7. Pinnell SR. Cutaneous photodamage oxidative stres and topical antioxidant protection. J Am Acad Dermatol. 2003;48:1-19. https://doi.org/10.1067/mjd.2003.16
• 8. Chu ECY. Treatment of vitiligo: medical treatment, phototherapy and surgical treatment. J.Dermatol Venereol 2009; 23:113-117.
• 9. Hass DT, Barnstable CJ. Uncoupling protein 2 in the glial response to stress: implications for neuroprotection. Neural Regen Res. 2016;11:1197-200. https://doi.org/ 10.4103/1673-5374.189159.
• 10. Pradhan R, Choudhary N, Mukherjee S, Chatterjee G, Ghosh A, et al. Can systemically generated reactive oxygen species help to monitor disease activity in generalized vitiligo? A pilot study. Indian J Dermatol. 2014;59:547-51. https://doi.org/10.4103/0019-5154.143506.
• 11. Yildirim M, Baysal V, Inaloz H.S, Can M. The role of oxidants and antioxidants in generalized vitiligo at tissue level. J Eur Acad Dermatol Venereol. 2004;18: 683-6. https://doi.org/10.1111/j.1468-3083.2004.01080.x
• 12. Sandeep K. Vashist, John H.T. Luong. Handbook of Immunoassay Technologies, 2018
• 13. Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE; Vitiligo Working Group. New discoveries in the pathogenesis and classification of vitiligo. J Am Acad Dermatol. 2017;77:1-13. https://doi.org/10.1016/j.jaad.2016.10.048.
• 14. S Li, M Xu, Q Niu, S Xu, Y Ding, Y Yan, et al. Efficacy of procyanidins against in vivo cellular oxidative damage: a systematic review and meta-analysis. PLoS ONE 2015;10:e0139455. https://doi.org/10.1371/journal.pone.0139455
• 15. Laddha NC, Dwivedi M, Mansuri MS, Gani AR, Ansarullah M, Ramachandran AV,et al. Vitiligo: interplay between oxidative stress and immune system. Exp Dermatol. 2013;22:245-50. https://doi.org/10.1111/exd.12103
• 16. Agrawal, S, Kumar, A, Dhali, TK. Majhi SK. Comparison of oxidant‐antioxidant status in patients with vitiligo and healthy population. Kathmandu Univ Med J . 2014;12:132-6. https://doi.org/10.3126/kumj.v12i2.13660
• 17. Shi MH, Wu Y, Li L, Cai YF, Liu M, Gao XH, 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
• 18. Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta. 2003;329:23-38. https://doi.org/10.1016/s0009-8981(03)00003-2.
• 19. Whongsiri P, Phoyen S, Boonla C. Oxidative Stress in Urothelial Carcinogenesis: Measurements of Protein Carbonylation and Intracellular Production of Reactive Oxygen Species. Methods Mol Biol. 2018;1655:109-17. https://doi.org/10.1007/978-1-4939-7234-0_9.
• 20. Datta S, Kundu S, Ghosh P, De S, Ghosh A, Chatterjee M. Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid arthritis. Clin Rheumatol. 2014;33:1557-64. https://doi.org/10.1007/s10067-014-2597-z.
• 21. Helbock HJ, Beckman KB, Ames BN. 8-Hydroxydeoxyguanosine and 8-Hydroxy-guanine as biomarkers of oxidative DNA damage. Methods Enzymol 1999;300:156-66. https://doi.org/10.1016/S0076-6879(99)00123-8
• 22. Lee HT, Lin CS, Lee CS, Tsai CY, Wei YH. Increased 8-hydroxy-2'-deoxyguanosine in plasma and decreased mRNA expression of human 8-oxoguanine DNA glycosylase 1, anti-oxidant enzymes, mitochondrial biogenesis-related proteins and glycolytic enzymes in leucocytes in patients with systemic lupus erythematosus. Clin Exp Immunol. 2014;176:66-77. https://doi.org/10.1111/cei.12256.
• 23. 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.
• 24. Vaseghi H, Houshmand M, Jadali Z. Increased levels of mitochondrial DNA copy number in patients with vitiligo. Clin Exp Dermatol. 2017;42:749-54. https://doi.org/10.1111/ced.13185.
• 25. Bhattacharya R, Singh P, John JJ, Gujar NL. Oxidative damage mediated iNOS and UCP-2 upregulation in rat brain after sub-acute cyanide exposure: dose and time-dependent effects. Drug Chem Toxicol. 2018;3:1-8. https://doi.org/10.1080/ 01480545.2018.1451876
• 26. Broche B, Ben Fradj S, Aguilar E, Sancerni T, Bénard M, Makaci F, et al. Mitochondrial Protein UCP2 Controls Pancreas Development. Diabetes. 2018;67:78-84. https://doi.org/10.2337/db17-0118
• 27. Dando I, Pacchiana R, Pozza ED, Cataldo I, Bruno S, Conti P, et al. UCP2 inhibition induces ROS/Akt/mTOR axis: Role of GAPDH nuclear translocation in genipin/everolimus anticancer synergism. Free Radic Biol Med. 2017;113:176-89. https://doi.org/10.1016/j.freeradbiomed.2017.09.022.
• 28. Zhong X, He J, Zhang X, Li C, Tian X, Xia W, et al. UCP2 alleviates tubular epithelial cell apoptosis in lipopolysaccharide-induced acute kidney injury by decreasing ROS production. Biomed Pharmacother. 2019;115:108914. https://doi.org/10.1016/j.biopha.2019.108914.