{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:27:36Z","timestamp":1786444056200,"version":"build-2736575974"},"reference-count":114,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Gout is a crystal-induced inflammatory arthritis driven by hyperuricemia and monosodium urate (MSU) crystal deposition, yet urate burden alone does not explain why only a subset of hyperuricemic individuals develops clinical disease, why acute flares are usually self-limited, or why gout clusters with renal and cardiometabolic comorbidity. This structured narrative review uses a gout-specific redox-switch framework, defined as a context-dependent shift in uric acid biology according to concentration, compartment, crystallization state, xanthine oxidoreductase (XOR) activity, inflammatory priming, and disease stage rather than as a binary molecular event. We integrate evidence on XOR-derived reactive oxygen species (ROS), mitochondrial stress, NLRP3 inflammasome signaling, neutrophil oxidative responses, neutrophil extracellular traps (NETs), lipid peroxidation, and potential ferroptosis-related mechanisms. Evidence is classified into five categories: established, mechanistically supported, human-associative, conceptual, and emerging\/unvalidated. The available human data support lipid-peroxidation and ferroptosis-associated molecular signatures, but do not yet establish ferroptotic cell death as a driver of gout. Therapeutic implications are therefore framed conservatively: urate-lowering therapy remains foundational, whereas redox-directed approaches require pathway specificity, disease-stage definition, and biomarker validation. The redox-switch concept is proposed as an organizing framework for mechanistic and translational research, not as a validated clinical algorithm.<\/jats:p>","DOI":"10.3390\/antiox15080993","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T09:11:16Z","timestamp":1786439476000},"page":"993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uric Acid as a Redox Switch in Gout: Linking Xanthine Oxidoreductase-Derived ROS, NLRP3 Inflammasome Activation and Emerging Ferroptotic Mechanisms"],"prefix":"10.3390","volume":"15","author":[{"given":"Petar-Preslav","family":"Petrov","sequence":"first","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delyan","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8751-8376","authenticated-orcid":false,"given":"Darina","family":"Barbutska","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zlatina","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Department of Midwifery Care, Faculty of Public Health, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4140-993X","authenticated-orcid":false,"given":"Nikoleta","family":"Dimitrova","sequence":"additional","affiliation":[{"name":"Department of Occupational Diseases Including Clinical Allergology Activities, University Multiprofile Hospital for Active Treatment \u201cSt. George\u201d, 4002 Plovdiv, Bulgaria"},{"name":"Department of Occupational Diseases, Clinical Allergology and Toxicology, Faculty of Medicine, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Gout Collaborators (2024). Global, regional, and national burden of gout, 1990\u20132020, and projections to 2050: A systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol., 6, e507\u2013e517."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41572-019-0115-y","article-title":"Gout","volume":"5","author":"Dalbeth","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1016\/S0140-6736(21)00569-9","article-title":"Gout","volume":"397","author":"Dalbeth","year":"2021","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41584-020-0441-1","article-title":"Global epidemiology of gout: Prevalence, incidence, treatment patterns and risk factors","volume":"16","author":"Dehlin","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Asghari, K.M., Zahmatyar, M., Seyedi, F., Motamedi, A., Zolfi, M., Alamdary, S.J., Fazlollahi, A., Shamekh, A., Mousavi, S.E., and Nejadghaderi, S.A. (2024). Gout: Global epidemiology, risk factors, comorbidities and complications: A narrative review. BMC Musculoskelet. Disord., 25.","DOI":"10.1186\/s12891-024-08180-9"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1007\/s10067-026-08050-w","article-title":"Global trends in age at onset of gout, 1990\u20132023: A sex-stratified and forecast analysis of the Global Burden of Disease Study 2023","volume":"45","author":"Rastogi","year":"2026","journal-title":"Clin. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e346","DOI":"10.1016\/S2665-9913(25)00344-3","article-title":"Worldwide trends in hyperuricaemia from 2000 to 2023: A systematic review and modelling analysis","volume":"8","author":"Nkeck","year":"2026","journal-title":"Lancet Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4497","DOI":"10.1007\/s10067-026-08180-1","article-title":"The rising global burden of gout attributable to kidney dysfunction: A 30-year trend analysis and projections to 2036","volume":"45","author":"Du","year":"2026","journal-title":"Clin. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/acr.24180","article-title":"2020 American College of Rheumatology Guideline for the Management of Gout","volume":"72","author":"FitzGerald","year":"2020","journal-title":"Arthritis Care Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1136\/annrheumdis-2016-209707","article-title":"2016 updated EULAR evidence-based recommendations for the management of gout","volume":"76","author":"Richette","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature04516","article-title":"Gout-associated uric acid crystals activate the NALP3 inflammasome","volume":"440","author":"Martinon","year":"2006","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.tibs.2016.09.002","article-title":"Mechanism and regulation of NLRP3 inflammasome activation","volume":"41","author":"He","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/ar2952","article-title":"Mechanisms of inflammation in gout","volume":"12","author":"Busso","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrrheum.2017.155","article-title":"Inflammation in gout: Mechanisms and therapeutic targets","volume":"13","author":"So","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_15","first-page":"39","article-title":"The role of the NLRP3 inflammasome in gout","volume":"4","author":"Kingsbury","year":"2011","journal-title":"J. Inflamm. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.molmed.2017.06.005","article-title":"Molecular pathophysiology of gout","volume":"23","author":"Desai","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1080\/15257770802138558","article-title":"Uric acid: The oxidant-antioxidant paradox","volume":"27","author":"Sautin","year":"2008","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5049\/EBP.2014.12.1.1","article-title":"Uric acid puzzle: Dual role as antioxidant and pro-oxidant","volume":"12","author":"Kang","year":"2014","journal-title":"Electrolyte Blood Press."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7378","DOI":"10.1038\/s41598-021-86962-0","article-title":"Uric acid shown to contribute to increased oxidative stress level independent of xanthine oxidoreductase activity in MedCity21 health examination registry","volume":"11","author":"Kurajoh","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/s41440-024-02031-9","article-title":"Current updates and future perspectives in uric acid research, 2024","volume":"48","author":"Kuwabara","year":"2025","journal-title":"Hypertens. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1136\/annrheumdis-2014-205304","article-title":"Hyperuricaemia and gout: Time for a new staging system?","volume":"73","author":"Dalbeth","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chhana, A., Lee, G., and Dalbeth, N. (2015). Factors influencing the crystallization of monosodium urate: A systematic literature review. BMC Musculoskelet. Disord., 16.","DOI":"10.1186\/s12891-015-0762-4"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/nature01991","article-title":"Molecular identification of a danger signal that alerts the immune system to dying cells","volume":"425","author":"Shi","year":"2003","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1172\/JCI28075","article-title":"MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals","volume":"116","author":"Chen","year":"2006","journal-title":"J. Clin. Invest."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.immuni.2008.09.013","article-title":"Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells","volume":"29","author":"Ng","year":"2008","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Liu, Y.R., Wang, J.Q., and Li, J. (2023). Role of NLRP3 in the pathogenesis and treatment of gout arthritis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1137822"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cao, D., Pu, H., Yuan, X., Li, Z., Yu, X., and Shi, X. (2026). The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1761121"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yan, H., Xiao, N., Yang, B., Zhang, J., Xu, Y., Chen, B., Zeng, S., Qian, H., Zhao, S., and Wang, R. (2026). Ferroptosis in gouty arthritis: A potential therapeutic strategy. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1769719"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/art.43215","article-title":"Gout and NLRP3 inflammasome biology","volume":"77","author":"Poulsen","year":"2025","journal-title":"Arthritis Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sies, H. (2020). Oxidative stress: Concept and some practical aspects. Antioxidants, 9.","DOI":"10.3390\/antiox9090852"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lichtenberg, D., Pinchuk, I., Yonassi, E., Weber, D., and Grune, T. (2023). Oxidative stress is a concept, not an indication for selective antioxidant treatment. Antioxidants, 12.","DOI":"10.3390\/antiox12061188"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41573-021-00233-1","article-title":"Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy","volume":"20","author":"Forman","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1089\/ars.2015.6317","article-title":"Clinical relevance of biomarkers of oxidative stress","volume":"23","author":"Frijhoff","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1089\/ars.2006.8.1865","article-title":"Redefining oxidative stress","volume":"8","author":"Jones","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s42255-022-00591-z","article-title":"Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo","volume":"4","author":"Murphy","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nm.3547","article-title":"Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines","volume":"20","author":"Schauer","year":"2014","journal-title":"Nat. Med."},{"key":"ref_38","first-page":"2272","article-title":"Mechanism of neutrophil extracellular traps in the pathogenesis of gout","volume":"42","author":"Chen","year":"2024","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13075-021-02472-4","article-title":"Neutrophil extracellular trap clearance by synovial macrophages in gout","volume":"23","author":"Jeong","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, F., Tie, N., Jin, Y., and Li, H. (2026). Neutrophil extracellular traps in gout: From immune defense to pathological dynamic equilibrium. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1826191"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/s41392-024-01916-y","article-title":"Hyperuricemia and its related diseases: Mechanisms and advances in therapy","volume":"9","author":"Du","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"RP96962","DOI":"10.7554\/eLife.96962.3","article-title":"Functional identification of soluble uric acid as an endogenous inhibitor of CD38","volume":"13","author":"Wen","year":"2024","journal-title":"eLife"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Yang, Y., Wu, Z., An, Z., and Li, S. (2024). Association between oxidative balance score and serum uric acid and hyperuricemia: A population-based study from the NHANES (2011\u20132018). Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1414075"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.1007\/s10067-026-08177-w","article-title":"Association between systemic oxidative stress imbalance and inflammatory markers in gouty patients: A cross-sectional case-control study in Yemen","volume":"45","author":"Alqadhi","year":"2026","journal-title":"Clin. Rheumatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nature742","article-title":"Molecular identification of a renal urate-anion exchanger that regulates blood urate levels","volume":"417","author":"Enomoto","year":"2002","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5ra11","DOI":"10.1126\/scitranslmed.3000237","article-title":"Common defects of ABCG2, a high-capacity urate exporter, cause gout: A function-based genetic analysis in a Japanese population","volume":"1","author":"Matsuo","year":"2009","journal-title":"Sci. Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1002\/art.39254","article-title":"2015 Gout classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"67","author":"Neogi","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41584-018-0004-x","article-title":"An update on the genetics of hyperuricaemia and gout","volume":"14","author":"Major","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6555","DOI":"10.1038\/ncomms7555","article-title":"Xanthine oxidoreductase regulates macrophage IL1\u03b2 secretion upon NLRP3 inflammasome activation","volume":"6","author":"Ives","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1093\/ibd\/izaf231","article-title":"Xanthine Oxidase-Dependent Activation of NLPR3 Inflammasome in Epithelial Cells Sustains Inflammation in Inflammatory Bowel Disease","volume":"31","author":"Fais","year":"2025","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17314","DOI":"10.1038\/s41598-019-53965-x","article-title":"Febuxostat, a xanthine oxidoreductase inhibitor, decreases NLRP3-dependent inflammation in macrophages by activating the purine salvage pathway and restoring cellular bioenergetics","volume":"9","author":"Nomura","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e202403191","DOI":"10.26508\/lsa.202403191","article-title":"Inhibition of xanthine oxidoreductase with febuxostat, but not allopurinol, prevents inflammasome assembly and IL-1\u03b2 release","volume":"8","author":"Archambault","year":"2025","journal-title":"Life Sci. Alliance"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1124\/pr.58.1.6","article-title":"Therapeutic effects of xanthine oxidase inhibitors: Renaissance half a century after the discovery of allopurinol","volume":"58","author":"Pacher","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"24598","DOI":"10.1038\/s41598-024-74154-5","article-title":"Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators","volume":"14","author":"Sanchez","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1016\/j.celrep.2017.02.004","article-title":"\u03b2-Hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flares","volume":"18","author":"Goldberg","year":"2017","journal-title":"Cell Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Chu, J., Tian, J., Li, P., Fu, D., Guo, L., and Sun, R. (2024). The impact of AIM2 inflammasome-induced pyroptosis on acute gouty arthritis and asymptomatic hyperuricemia patients. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1386939"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nri3452","article-title":"Activation and regulation of the inflammasomes","volume":"13","author":"Latz","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/ni.1631","article-title":"Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization","volume":"9","author":"Hornung","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"787","DOI":"10.4049\/jimmunol.0901363","article-title":"Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression","volume":"183","author":"Bauernfeind","year":"2009","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1136\/annrheumdis-2014-206564","article-title":"Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra","volume":"75","author":"Crisan","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"156502","DOI":"10.1016\/j.cyto.2024.156502","article-title":"Soluble urate-induced effects on cytokine production in vitro\u2014Assessment of methodologies and cell types","volume":"175","author":"Liu","year":"2024","journal-title":"Cytokine"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ni.1831","article-title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","volume":"11","author":"Zhou","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/ni.1980","article-title":"Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome","volume":"12","author":"Nakahira","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_65","first-page":"300","article-title":"Monosodium urate crystals exposure is associated with limited transcriptional changes in primary human PBMCs","volume":"63","author":"Nica","year":"2025","journal-title":"Rom. J. Intern. Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Nica, V., Gaal, O., Badii, M., Cab\u0103u, G., Mirea, A.-M., Hotea, I., Pamfil, C., Rednic, S., Popp, R.A., and Netea, M.G. (2025). Gout risk allele regulating IRF5 expression is associated with enhanced IL-1\u03b2 production in response to palmitate and monosodium urate crystals. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202509.2154.v1"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3317307","DOI":"10.1155\/2023\/3317307","article-title":"P2X7R mediates the synergistic effect of ATP and MSU crystals to induce acute gouty arthritis","volume":"2023","author":"Li","year":"2023","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"39884","DOI":"10.1038\/srep39884","article-title":"Soluble uric acid activates the NLRP3 inflammasome","volume":"7","author":"Braga","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1038\/s41440-023-01391-y","article-title":"Inhibition of the uric acid efflux transporter ABCG2 enhances stimulating effect of soluble uric acid on IL-1\u03b2 production in murine macrophage-like J774.1 cells","volume":"46","author":"Notsu","year":"2023","journal-title":"Hypertens. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1038\/s41440-026-02601-z","article-title":"Soluble uric acid enhances gouty inflammation via activating gene expression related to innate immune responses, M1 macrophage polarization and urate crystal phagocytosis in mouse macrophage-like cells: Novel insights into its mechanisms from RNA sequencing","volume":"49","author":"Notsu","year":"2026","journal-title":"Hypertens. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.freeradbiomed.2024.09.009","article-title":"Neutrophil extracellular traps promote M1 macrophage polarization in gouty inflammation via targeting hexokinase-2","volume":"224","author":"Tan","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107007","DOI":"10.1016\/j.imlet.2025.107007","article-title":"NETs activate AIM2 to mediate synovial fibroblast pyroptosis and promote acute gouty arthritis development","volume":"275","author":"Tian","year":"2025","journal-title":"Immunol. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12950-024-00423-9","article-title":"Resolution of acute inflammation induced by monosodium urate crystals (MSU) through neutrophil extracellular trap-MSU aggregate-mediated negative signaling","volume":"21","author":"Lu","year":"2024","journal-title":"J. Inflamm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.molmed.2024.05.010","article-title":"Neutrophils and extracellular traps in crystal-associated diseases","volume":"30","author":"Ma","year":"2024","journal-title":"Trends Mol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Huang, S., Wang, Y., Lin, S., Guan, W., Liang, H., and Shen, J. (2023). Neutrophil autophagy induced by monosodium urate crystals facilitates neutrophil extracellular traps formation and inflammation remission in gouty arthritis. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1071630"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e003586","DOI":"10.1136\/rmdopen-2023-003586","article-title":"Spontaneous resolution of acute gout: Mechanisms and therapeutic targets","volume":"9","author":"Shi","year":"2023","journal-title":"RMD Open"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1080\/03009742.2025.2491176","article-title":"Non-inflammatory macrophages phagocytose and hydrolyse monosodium urate crystals in different stages of gout","volume":"54","author":"Huang","year":"2025","journal-title":"Scand. J. Rheumatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.2147\/JIR.S460333","article-title":"Targeting neutrophil extracellular traps in gouty arthritis: Insights into pathogenesis and therapeutic potential","volume":"17","author":"Li","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Liu, C., Zhou, M., Jiang, W., Ye, S., Tian, S., Jiang, C., Hao, K., Li, H., and Hu, Q. (2022). GPR105-targeted therapy promotes gout resolution as a switch between NETosis and apoptosis of neutrophils. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.870183"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: Molecular mechanisms and health implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Bieri, S., M\u00f6ller, B., and Amsler, J. (2024). Ferroptosis in Arthritis: Driver of the Disease or Therapeutic Option?. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158212"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition","volume":"13","author":"Doll","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nchembio.2238","article-title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis","volume":"13","author":"Kagan","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1038\/s41589-019-0408-1","article-title":"The chemical basis of ferroptosis","volume":"15","author":"Conrad","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wang, J., Lin, Y., Liu, N., Hu, M., and Zhang, M. (2024). Differential expression of ferroptosis-related proteins in urinary exosomes: Potential indicators for monitoring acute gout attack. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1476631"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Xiao, N., Lu, H., Zeng, S., Yan, H., Yang, Q., Sheng, L., Chen, B., Xu, Y., Zhang, J., and Xie, J. (2026). Exploring the inflammatory origins of gouty arthritis: Mechanistic studies based on local lesion proteomics and validation. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1764497"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Geng, Z., Wu, D., Hou, Y., Kang, L., Zhang, X., Feng, Z., Song, J., Chen, D., Zhang, T., and Xu, L. (Clin. Rheumatol., 2026). Monosodium urate crystals induce lytic macrophage death partially dependent on both pyroptosis and necroptosis, Clin. Rheumatol., advance online publication.","DOI":"10.1007\/s10067-026-08262-0"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"117874","DOI":"10.1016\/j.bmc.2024.117874","article-title":"Recent advances in the treatment of gout with NLRP3 inflammasome inhibitors","volume":"112","author":"Tian","year":"2024","journal-title":"Bioorg. Med. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Shao, B.Z., Xu, Z.Q., Han, B.Z., Su, D.F., and Liu, C. (2015). NLRP3 inflammasome and its inhibitors: A review. Front. Pharmacol., 6.","DOI":"10.3389\/fphar.2015.00262"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s43856-026-01590-x","article-title":"A broad cathepsin inhibitor blocks crystal-stimulated inflammasome-dependent and -independent inflammation and gout arthritis","volume":"6","author":"Orellano","year":"2026","journal-title":"Commun. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of Nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"101107","DOI":"10.1016\/j.redox.2019.101107","article-title":"NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis","volume":"23","author":"Dodson","year":"2019","journal-title":"Redox Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"115957","DOI":"10.1016\/j.biopha.2023.115957","article-title":"Activation of Nrf2 antioxidant signaling alleviates gout arthritis pain and inflammation","volume":"170","author":"Zeng","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1007\/s12026-024-09548-8","article-title":"Phillyrin inhibits oxidative stress and neutrophil extracellular trap formation through the KEAP1\/NRF2 pathway in gouty arthritis","volume":"72","author":"Xu","year":"2024","journal-title":"Immunol. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"155754","DOI":"10.1016\/j.phymed.2024.155754","article-title":"Astilbin inhibited neutrophil extracellular traps in gouty arthritis through suppression of purinergic P2Y6 receptor","volume":"130","author":"Li","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Catal\u00e1n, L., Carceller, M.C., Terencio, M.C., Alcaraz, M.J., Ferr\u00e1ndiz, M.L., and Montesinos, M.C. (2024). Osteostatin mitigates gouty arthritis through the inhibition of caspase-1 activation and upregulation of Nrf2 expression. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052752"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.7150\/thno.95611","article-title":"Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis","volume":"14","author":"Yin","year":"2024","journal-title":"Theranostics"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Lin, Y., Luo, T., Weng, A., Huang, X., Yao, Y., Fu, Z., Li, Y., Liu, A., Li, X., and Chen, D. (2020). Gallic acid alleviates gouty arthritis by inhibiting NLRP3 inflammasome activation and pyroptosis through enhancing Nrf2 signaling. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.580593"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6718","DOI":"10.1002\/jcb.27969","article-title":"Curcumin ameliorates monosodium urate-induced gouty arthritis through Nod-like receptor 3 inflammasome mediation via inhibiting nuclear factor-kappa B signaling","volume":"120","author":"Li","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.jsps.2022.04.013","article-title":"A review on benefits of quercetin in hyperuricemia and gouty arthritis","volume":"30","author":"Nutmakul","year":"2022","journal-title":"Saudi Pharm. J."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Wu, C., Li, F., Zhang, X., Xu, W., Wang, Y., Yao, Y., Han, Z., and Xia, D. (2022). (-)-Epicatechin ameliorates monosodium urate-induced acute gouty arthritis through inhibiting NLRP3 inflammasome and the NF-\u03baB signaling pathway. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.799552"},{"key":"ref_105","first-page":"8868527","article-title":"Cichoric acid ameliorates monosodium urate-induced inflammatory response by reducing NLRP3 inflammasome activation via inhibition of NF-\u03baB signaling pathway","volume":"2021","author":"Wang","year":"2021","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/cmi.2014.65","article-title":"Monosodium urate crystals trigger Nrf2- and heme oxygenase-1-dependent inflammation in THP-1 cells","volume":"12","author":"Jhang","year":"2015","journal-title":"Cell. Mol. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/rheumatology\/kex499","article-title":"Suppression of NLRP3 inflammasome by oral treatment with sulforaphane alleviates acute gouty inflammation","volume":"57","author":"Yang","year":"2018","journal-title":"Rheumatology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1002\/acr.20519","article-title":"Effect of oral vitamin C supplementation on serum uric acid: A meta-analysis of randomized controlled trials","volume":"63","author":"Juraschek","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1002\/art.37925","article-title":"Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: A pilot randomized controlled trial","volume":"65","author":"Stamp","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1001\/archinternmed.2008.606","article-title":"Vitamin C intake and the risk of gout in men: A prospective study","volume":"169","author":"Choi","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Yan, H., Yang, B., Xiao, N., Zhang, J., Xu, Y., Chen, B., Zeng, S., Qian, H., Zhao, S., and Wang, R. (2026). From uric acid to tophi: Multistage molecular and cellular mechanisms of tophi formation. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1847953"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Ohashi, Y., Ooyama, H., Makinoshima, H., Takada, T., Matsuo, H., and Ichida, K. (2024). Plasma and urinary metabolomic analysis of gout and asymptomatic hyperuricemia and profiling of potential biomarkers: A pilot study. Biomedicines, 12.","DOI":"10.3390\/biomedicines12020300"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Sun, W., Xu, L., Chen, H., Sun, M., Li, Z., Li, R., Ma, L., Zhang, H., Ji, A., and He, Y. (Arthritis Rheumatol., 2026). A metabolomic signature predicts gout flare clinical outcome associated with colchicine prophylaxis, Arthritis Rheumatol., advance online publication.","DOI":"10.1002\/art.70094"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s11306-026-02501-w","article-title":"A machine learning approach to metabolomics identifies putative biomarker candidates and dysregulated pathways for distinguishing gout from asymptomatic hyperuricemia in the Zhuang population","volume":"22","author":"Wei","year":"2026","journal-title":"Metabolomics"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/8\/993\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T09:28:20Z","timestamp":1786440500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/8\/993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":114,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["antiox15080993"],"URL":"https:\/\/doi.org\/10.3390\/antiox15080993","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}