{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:24:08Z","timestamp":1790886248700,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the University of Medicine and Pharmacy Carol Davila"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune reaction. However, other pathogenic pathways complement these mechanisms. Recent studies highlight the involvement of nitrosative stress in the pathogenesis of chronic inflammatory skin diseases. Current data on its role in the pathogenesis of LP are scarce. Methods: In this article, we investigated nitrosative stress in 40 cutaneous LP (CLP) patients compared to 40 healthy subjects using serum markers including nitrosative stress markers\u2014direct nitrite, total nitrite, nitrate and symmetric dimethylarginine (SDMA), total antioxidant status (TAS), and hsCRP, a marker of inflammation, and analyzed the relationship between nitrosative stress, antioxidant defense, and inflammation to offer new insights into the role of the NO pathway in LP pathogenesis. Results: We identified significantly higher serum levels of direct nitrite, total nitrite, nitrate, SDMA and hsCRP, and significantly lower levels of TAS in CLP patients versus controls. There were significant negative correlations between the serum levels of TAS and significantl positive correlations between the serum levels of hsCRP and the analyzed nitrosative stress markers in patients with CLP. Conclusion: Our results indicate an increased level of nitrosative stress in LP patients that correlates with a pro-inflammatory status and altered antioxidant defense.<\/jats:p>","DOI":"10.3390\/antiox13060670","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T10:06:01Z","timestamp":1717409161000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Interplay between Nitrosative Stress, Inflammation, and Antioxidant Defense in Patients with Lichen Planus"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4983-7648","authenticated-orcid":false,"given":"Mircea","family":"Tampa","sequence":"first","affiliation":[{"name":"Department of Dermatology, \u2018Carol Davila\u2019 University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Dermatology, \u2018Victor Babes\u2019 Clinical Hospital for Infectious Diseases, 030303 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilinca","family":"Nicolae","sequence":"additional","affiliation":[{"name":"Department of Dermatology, \u2018Victor Babes\u2019 Clinical Hospital for Infectious Diseases, 030303 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina Daniela","family":"Ene","sequence":"additional","affiliation":[{"name":"Departments of Nephrology, \u2018Carol Davila\u2019 University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Nephrology, \u2018Carol Davila\u2019 Nephrology Hospital, 010731 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Iulia","family":"Mitran","sequence":"additional","affiliation":[{"name":"Department of Microbiology, \u2018Carol Davila\u2019 University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina Irina","family":"Mitran","sequence":"additional","affiliation":[{"name":"Department of Microbiology, \u2018Carol Davila\u2019 University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Matei","sequence":"additional","affiliation":[{"name":"Department of Dermatology, \u2018Carol Davila\u2019 University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Roxana","family":"Georgescu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, \u2018Carol Davila\u2019 University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Dermatology, \u2018Victor Babes\u2019 Clinical Hospital for Infectious Diseases, 030303 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.18203\/issn.2455-4529.IntJResDermatol20164007","article-title":"Study of Oxidative Stress in Patients of Psoriasis","volume":"2","author":"Kaur","year":"2016","journal-title":"Int. J. Res. Dermatol."},{"key":"ref_2","first-page":"864","article-title":"Lichen Planus\u2014A Clinical Guide","volume":"19","author":"Solimani","year":"2021","journal-title":"J. Dtsch. Dermatol. Ges. J. Ger. Soc. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"737813","DOI":"10.3389\/fmed.2021.737813","article-title":"Lichen Planus","volume":"8","author":"Boch","year":"2021","journal-title":"Front. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/j.1834-7819.2002.tb00540.x","article-title":"Oral Lichen Planus: Causes, Diagnosis and Management","volume":"47","author":"Sugerman","year":"2002","journal-title":"Aust. Dent. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1177\/154411130201300405","article-title":"The Pathogenesis of Oral Lichen Planus","volume":"13","author":"Sugerman","year":"2002","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S158","DOI":"10.4103\/0975-7406.155873","article-title":"Oral Lichen Planus: An Overview","volume":"7","author":"Krupaa","year":"2015","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vi\u010di\u0107, M., Hla\u010da, N., Ka\u0161telan, M., Brajac, I., Soto\u0161ek, V., and Prpi\u0107 Massari, L. (2023). Comprehensive Insight into Lichen Planus Immunopathogenesis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24033038"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"635021","DOI":"10.3389\/fimmu.2021.635021","article-title":"Reactive Oxygen Species in Autoimmune Cells: Function, Differentiation, and Metabolism","volume":"12","author":"Lin","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kassab, A., Khalij, Y., Ayed, Y., Dar-Odeh, N., Kokandi, A.A., Denguezli, M., and Youssef, M. (2023). Serum Inflammatory and Oxidative Stress Markers in Patients with Vitiligo. J. Clin. Med., 12.","DOI":"10.3390\/jcm12185861"},{"key":"ref_10","first-page":"522","article-title":"Oxidative Stress-Related Markers and Alopecia Areata through Latex Turbidimetric Immunoassay Method","volume":"53","author":"Georgescu","year":"2016","journal-title":"Mater. Plast."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"154569","DOI":"10.1016\/j.prp.2023.154569","article-title":"Oxidative Stress Markers in the Saliva of Patients with Oral Lichen Planus","volume":"248","author":"Gonzaga","year":"2023","journal-title":"Pathol.-Res. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rezazadeh, F., Mahdavi, D., Fassihi, N., Sedarat, H., Tayebi Khorami, E., and Tabesh, A. (2023). Evaluation of the Salivary Level of Glutathione Reductase, Catalase and Free Thiol in Patients with Oral Lichen Planus. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-03242-1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1030893","DOI":"10.3389\/fphar.2022.1030893","article-title":"Antioxidant Therapy for Patients with Oral Lichen Planus: A Systematic Review and Meta-Analysis","volume":"13","author":"Bao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Georgescu, S.R., Mitran, C.I., Mitran, M.I., Nicolae, I., Matei, C., Ene, C.D., Popa, G.L., and Tampa, M. (2021). Oxidative Stress in Cutaneous Lichen Planus\u2014A Narrative Review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10122692"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41531-022-00370-3","article-title":"Nitrosative Stress in Parkinson\u2019s Disease","volume":"8","author":"Stykel","year":"2022","journal-title":"npj Park. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, F., Yuan, Q., Chen, F., Pang, J., Pan, C., Xu, F., and Chen, Y. (2021). Fundamental Mechanisms of the Cell Death Caused by Nitrosative Stress. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.742483"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kr\u00f3l, M., and Kepinska, M. (2020). Human Nitric Oxide Synthase\u2014Its Functions, Polymorphisms, and Inhibitors in the Context of Inflammation, Diabetes and Cardiovascular Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010056"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.mad.2017.08.018","article-title":"The Role of Nitric Oxide in Diabetic Skin (Patho)Physiology","volume":"172","author":"Stancic","year":"2018","journal-title":"Mech. Ageing Dev."},{"key":"ref_19","first-page":"48","article-title":"Evaluation of Serum Nitric Oxide Level in Patients with Oral Lichen Planus","volume":"15","author":"Mehdipour","year":"2014","journal-title":"J. Dent."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1600-0714.1999.tb02053.x","article-title":"Elevated Production of Salivary Nitric Oxide in Oral Mucosal Diseases","volume":"28","author":"Ohashi","year":"1999","journal-title":"J. Oral Pathol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bryan, N.S., and Grisham, M.B. (2007). Methods to Detect Nitric Oxide and its Metabolites in Biological Samples. Free Radic. Biol. Med., 43.","DOI":"10.1016\/j.freeradbiomed.2007.04.026"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00359","DOI":"10.1016\/j.plabm.2024.e00359","article-title":"Comparison of Two Methods for Dimethylarginines Quantification","volume":"39","author":"Prokop","year":"2024","journal-title":"Pract. Lab. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e13624","DOI":"10.1111\/and.13624","article-title":"Total Antioxidant Capacity\u2014Relevance, Methods and Clinical Implications","volume":"53","author":"Gupta","year":"2021","journal-title":"Andrologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9914652","DOI":"10.1155\/2021\/9914652","article-title":"Systematic Review and Meta-Analysis of Oxidative Stress and Antioxidant Markers in Oral Lichen Planus","volume":"2021","author":"Wang","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Settelmeier, S., Rassaf, T., Hendgen-Cotta, U.B., and Stoffels, I. (2021). Nitric Oxide Generating Formulation as an Innovative Approach to Topical Skin Care: An Open-Label Pilot Study. Cosmetics, 8.","DOI":"10.3390\/cosmetics8010016"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1111\/bph.13673","article-title":"Biomarkers of Oxidative and Nitro-Oxidative Stress: Conventional and Novel Approaches","volume":"174","author":"Zarkovic","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_27","first-page":"1045","article-title":"Potential Pathogenic Mechanisms Involved in the Association between Lichen Planus and Hepatitis C Virus Infection","volume":"17","author":"Georgescu","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"439","DOI":"10.4103\/0019-5154.159624","article-title":"Alterations in Lipid Metabolism and Antioxidant Status in Lichen Planus","volume":"60","author":"Panchal","year":"2015","journal-title":"Indian J. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13075-018-1530-2","article-title":"Autoimmune Reactivity to Malondialdehyde Adducts in Systemic Lupus Erythematosus is Associated with Disease Activity and Nephritis","volume":"20","author":"Hardt","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00418-020-01858-w","article-title":"Photochemistry of Nitric Oxide and S-Nitrosothiols in Human Skin","volume":"153","author":"Pelegrino","year":"2020","journal-title":"Histochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"938","DOI":"10.14336\/AD.2017.1207","article-title":"Nitrate and Nitrite in Health and Disease","volume":"9","author":"Ma","year":"2018","journal-title":"Aging Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7075","DOI":"10.1111\/jocd.15378","article-title":"Nitric Oxide Synthase Activity: A Novel Potential Biomarker for Predicting Alopecia Areata","volume":"21","author":"Taskin","year":"2022","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"624","DOI":"10.4103\/ijd.ijd_917_20","article-title":"Assessment of Oxidative\/Nitrosative Stress and Raftlin in Vitiligo","volume":"67","author":"Mulayim","year":"2022","journal-title":"Indian J. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/j.1365-2230.2007.02436.x","article-title":"Lipid Peroxidation and Antioxidant Status in Lichen Planus","volume":"32","author":"Sezer","year":"2007","journal-title":"Clin. Exp. Dermatol. Clin. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jssdds.2012.12.002","article-title":"Evaluation of the Antioxidant Status in Patients of Lichen Planus in Kashmir Valley\u2014A Hospital Based Study","volume":"17","author":"Hassan","year":"2013","journal-title":"J. Saudi Soc. Dermatol. Dermatol. Surg."},{"key":"ref_36","first-page":"3","article-title":"Oxidative Stress in Lichen Planus","volume":"19","author":"Aly","year":"2010","journal-title":"Acta Dermatoven APA"},{"key":"ref_37","first-page":"125","article-title":"Oxidative Stress in Classic Type Lichen Planus","volume":"32","author":"Ahmed","year":"2012","journal-title":"Bull. Egypt. Soc. Physiol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e14856","DOI":"10.1111\/exd.14856","article-title":"The Underestimated Role of Mitochondria in Vitiligo: From Oxidative Stress to Inflammation and Cell Death","volume":"33","author":"Lin","year":"2024","journal-title":"Exp. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kanda, N. (2021). Psoriasis: Pathogenesis, Comorbidities, and Therapy Updated. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062979"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1089\/ped.2019.1137","article-title":"Quercetin Improves Inflammation, Oxidative Stress, and Impaired Wound Healing in Atopic Dermatitis Model of Human Keratinocytes","volume":"33","author":"Beken","year":"2020","journal-title":"Pediatr. Allergy Immunol. Pulmonol."},{"key":"ref_41","first-page":"6","article-title":"Serum and Salivary Level of Nitric Oxide (NOx) and CRP in Oral Lichen Planus (OLP) Patients","volume":"21","author":"Shiva","year":"2020","journal-title":"J. Dent."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e82","DOI":"10.1590\/1807-3107bor-2018.vol32.0082","article-title":"Cytokines, Cortisol, and Nitric Oxide as Salivary Biomarkers in Oral Lichen Planus: A Systematic Review","volume":"32","author":"Humberto","year":"2018","journal-title":"Braz. Oral Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1007\/s10753-021-01615-8","article-title":"Regulatory Role of Nitric Oxide in Cutaneous Inflammation","volume":"45","author":"Man","year":"2022","journal-title":"Inflammation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.3233\/ADR-230054","article-title":"Comparing Symmetric Dimethylarginine and Amyloid-\u03b242 as Predictors of Alzheimer\u2019s Disease Development","volume":"7","author":"Goodman","year":"2023","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1159\/000507862","article-title":"Symmetric Dimethylarginine as a Secondary Prevention Biomarker of Chronic Kidney Disease","volume":"144","author":"Ostojic","year":"2020","journal-title":"Nephron"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1093\/ndt\/gfl292","article-title":"Symmetric Dimethylarginine (SDMA) as Endogenous Marker of Renal Function\u2014A Meta-Analysis","volume":"21","author":"Kielstein","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zinellu, A., Fois, A.G., Sotgia, S., Sotgiu, E., Zinellu, E., Bifulco, F., Mangoni, A.A., Pirina, P., and Carru, C. (2016). Arginines Plasma Concentration and Oxidative Stress in Mild to Moderate COPD. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160237"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.semnephrol.2014.02.003","article-title":"Dimethylarginines ADMA and SDMA: The Real Water-Soluble Small Toxins?","volume":"34","author":"Schepers","year":"2014","journal-title":"Semin. Nephrol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.2215\/CJN.01720211","article-title":"Symmetric Dimethylarginine as a Proinflammatory Agent in Chronic Kidney Disease","volume":"6","author":"Schepers","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/6\/670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:52Z","timestamp":1760107852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/6\/670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,30]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["antiox13060670"],"URL":"https:\/\/doi.org\/10.3390\/antiox13060670","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,30]]}}}