{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:31:35Z","timestamp":1786509095628,"version":"build-2736575974"},"reference-count":83,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005969","name":"University of Bologna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005969","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Ulcerative colitis is characterized by inflammation, oxidative stress, and excessive free radical production. This study investigated the antioxidant, anti-inflammatory, and protective effects of N-acetylcysteine (NAC), Tiron, and their fixed-ratio combination in acetic acid-induced colitis. An integrated approach was used, combining ligand\u2013ligand docking, acellular antioxidant and protein-denaturation assays, and an in vivo model in male Wistar rats. Colitis was induced by intrarectal administration of 3% acetic acid after 14 days of intraperitoneal pretreatment with NAC, Tiron, or NAC\u2013Tiron. Docking analysis suggested physicochemical compatibility through non-covalent interactions. In vitro, NAC, Tiron, and their combination showed antioxidant and anti-denaturation activities. NAC\u2013Tiron displayed greater activity than the individual compounds in selected endpoints, particularly 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, but did not consistently outperform them across the other assays. In vivo, NAC, Tiron, and NAC\u2013Tiron attenuated macroscopic and histological colonic damage, reduced inflammatory cell infiltration and edema, decreased lipid peroxidation and protein carbonylation, and helped preserve superoxide dismutase (SOD) activity, reduced glutathione (GSH), and total thiols. The treatments also attenuated increases in C-reactive protein (CRP) and free iron without evident worsening of the measured systemic biochemical parameters. Overall, these findings provide an exploratory proof of concept for fixed-ratio NAC\u2013Tiron co-administration but do not establish pharmacological synergy or superiority over standard therapies.<\/jats:p>","DOI":"10.3390\/ijms27167146","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:23:50Z","timestamp":1786357430000},"page":"7146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N-Acetylcysteine, Tiron, and Their Combination: In Vitro Antioxidant and Anti-Inflammatory Activities and Their Protective Effect in a Rat Model of Acetic Acid-Induced Ulcerative Colitis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1305-7965","authenticated-orcid":false,"given":"Ahmed","family":"Kouki","sequence":"first","affiliation":[{"name":"Environment Biomonitoring Laboratory (LR01\/ES14), Sciences Faculty of Bizerte, University of Carthage, Zarzouna, Bizerte 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-6043","authenticated-orcid":false,"given":"Dorsaf","family":"Bouzazi","sequence":"additional","affiliation":[{"name":"Cardiovascular Physiology and Pathophysiology Platform, Laboratory of Biomolecules, Venoms and Theranostic Applications, (LR20IPT01), Institut Pasteur of Tunis, Tunis El Manar University, Tunis 1068, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Trabelsi","sequence":"additional","affiliation":[{"name":"Environment Biomonitoring Laboratory (LR01\/ES14), Sciences Faculty of Bizerte, University of Carthage, Zarzouna, Bizerte 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Mbirki","sequence":"additional","affiliation":[{"name":"Laboratory of Integrated Physiology (LR17ES02), Faculty of Sciences of Bizerte, University of Carthage, Bizerte 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2458-216X","authenticated-orcid":false,"given":"Salwa","family":"Bouadballah","sequence":"additional","affiliation":[{"name":"Environment Biomonitoring Laboratory (LR01\/ES14), Sciences Faculty of Bizerte, University of Carthage, Zarzouna, Bizerte 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-9798","authenticated-orcid":false,"given":"Safia","family":"El-Bok","sequence":"additional","affiliation":[{"name":"Laboratory of Biodiversity, Biotechnologies and Climate Change (LR11\/ES09), Faculty of Sciences of Tunis, University of Tunis El-Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamouda","family":"Beyrem","sequence":"additional","affiliation":[{"name":"Environment Biomonitoring Laboratory (LR01\/ES14), Sciences Faculty of Bizerte, University of Carthage, Zarzouna, Bizerte 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Valerii","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8525-2981","authenticated-orcid":false,"given":"Enzo","family":"Spisni","sequence":"additional","affiliation":[{"name":"Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezzedine","family":"Aouani","sequence":"additional","affiliation":[{"name":"Laboratory of Bioactive Substances (LR03BBC15), Center of Biotechnology of Borj-Cedria, BP 901, Hammam-Lif 2050, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5368-4800","authenticated-orcid":false,"given":"Mossadok","family":"Ben-Attia","sequence":"additional","affiliation":[{"name":"Environment Biomonitoring Laboratory (LR01\/ES14), Sciences Faculty of Bizerte, University of Carthage, Zarzouna, Bizerte 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide Incidence and Prevalence of Inflammatory Bowel Disease in the 21st Century: A Systematic Review of Population-Based Studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12328-017-0813-5","article-title":"Gut Microbiota in the Pathogenesis of Inflammatory Bowel Disease","volume":"11","author":"Nishida","year":"2018","journal-title":"Clin. 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