{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:44:33Z","timestamp":1789767873230,"version":"4.0.1"},"reference-count":197,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82305145"],"award-info":[{"award-number":["82305145"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LQ23H270006"],"award-info":[{"award-number":["LQ23H270006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and the formation of immune complexes (ICs), which lead to widespread inflammation and tissue damage. Neutrophil extracellular traps (NETs), web-like structures composed of DNA, histones, and antimicrobial proteins released by activated neutrophils, play a crucial role in innate immunity by defending against pathogens. However, excessive NET formation and ineffective clearance of these structures contribute to the development of SLE. This review explores the mechanisms behind NET formation in SLE, their relationship with oxidative stress, and the potential role of antioxidants in treatment. Research indicates that SLE patients exhibit two key abnormalities: excessive NET formation and impaired NET clearance. Excessive NET formation is driven by proinflammatory low-density granulocytes (LDGs) and immune complexes (ICs). Impaired NET clearance stems from reduced DNase1\/DNase1L3 activity or anti-nuclease autoantibodies. These two abnormalities lead to elevated circulating NETs. These NETs act as autoantigen reservoirs, forming pathogenic NET\u2013ICs that amplify autoimmune responses. Oxidative stress drives NET formation by activating NADPH oxidase. In contrast, various antioxidants, including enzymatic and non-enzymatic types, can inhibit NET formation via scavenging reactive oxygen species (ROS) and blocking NADPH oxidase activation. Preclinical studies show that antioxidants such as curcumin, resveratrol, and mitochondrial-targeted MitoQ reduce NET formation and ameliorate lupus nephritis; clinical trials confirm that curcumin and N-acetylcysteine (NAC) lower SLE disease activity and reduce proteinuria, supporting their role as safe adjuvant therapies. However, high-dose vitamin E may exacerbate autoimmunity, highlighting the need for dose optimization. Future research should aim to clarify the mechanisms underlying NET formation in SLE and to optimize new antioxidant therapies, including assessments of their long-term efficacy and safety.<\/jats:p>","DOI":"10.3390\/antiox15010025","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T09:58:34Z","timestamp":1766570314000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Neutrophil Extracellular Traps in Systemic Lupus Erythematosus: Pathogenic Mechanisms, Crosstalk with Oxidative Stress, and Antioxidant Therapeutic Potential"],"prefix":"10.3390","volume":"15","author":[{"given":"Xi","family":"Chen","sequence":"first","affiliation":[{"name":"Jinhua Academy of Zhejiang Chinese Medical University, Jinhua 321000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Gao","sequence":"additional","affiliation":[{"name":"Jinhua Academy of Zhejiang Chinese Medical University, Jinhua 321000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Jinhua Academy of Zhejiang Chinese Medical University, Jinhua 321000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3749-4089","authenticated-orcid":false,"given":"Honghua","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China"},{"name":"Macquarie Medical School, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengping","family":"Wen","sequence":"additional","affiliation":[{"name":"Jinhua Academy of Zhejiang Chinese Medical University, Jinhua 321000, China"},{"name":"Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Innovative Research Center for Basic Medicine on Autoimmune Diseases, Ministry of Education, Hangzhou 310053, China"},{"name":"Science and Technology Innovation Center, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1997-1435","authenticated-orcid":false,"given":"Yujun","family":"Tang","sequence":"additional","affiliation":[{"name":"Jinhua Academy of Zhejiang Chinese Medical University, Jinhua 321000, China"},{"name":"Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Innovative Research Center for Basic Medicine on Autoimmune Diseases, Ministry of Education, Hangzhou 310053, China"},{"name":"Science and Technology Innovation Center, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shiozawa, S. 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