{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T01:49:10Z","timestamp":1776908950620,"version":"3.51.2"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: The safety of intraperitoneal mesh placement in contaminated fields remains controversial because of the increased risk of inflammation and adhesion formation. N-acetyl-L-cysteine (NAC) has antioxidant, pro-fibrinolytic and antibiofilm actions that could attenuate this response. The aim of this study is to determine whether NAC reduces mesh-related inflammation in a septic model created by intraperitoneal Escherichia coli (E.coli) inoculation. The primary comparison was prospectively defined between E. coli\u2013inoculated animals treated with NAC (D) and those without NAC (B). Groups without E. coli (A,C,E) are presented for context and were compared previously. Methods: In this randomized, double-blind experimental model (five groups, n = 20 per group), all rats underwent midline laparotomy with intraperitoneal placement of a composite mesh, followed by standardized ciprofloxacin administration. The septic groups received intraperitoneal E. coli, while the NAC-treated groups additionally received intraperitoneal NAC (150 mg\/kg). Serum levels of IL-1\u03b1, IL-6, and TNF-\u03b1 were measured on postoperative days 7, 14, and 21. On day 21, adhesions were graded using the Modified Diamond system, histology (inflammatory infiltration, fibrosis, neovascularization) was scored, and mesh cultures were obtained. Cytokine data were analyzed with repeated-measures ANOVA, while categorical or ordinal outcomes were assessed using \u03c72 or Fisher\u2019s exact tests with Bonferroni-adjusted pairwise comparisons. Results: E. coli inoculation significantly increased adhesion burden and worsened histologic scores compared with controls (both p &lt; 0.001). NAC administration in the septic model significantly reduced adhesions and improved all histologic domains relative to E. coli alone (all p \u2264 0.003), with values comparable to controls (non-significant across domains). For cytokines, there was a significant overall group effect for IL-1\u03b1, IL-6, and TNF-\u03b1 (all p &lt; 0.001), without a main effect of time or time \u00d7 group interaction. Pairwise contrasts showed lower IL-1\u03b1 (p = 0.024), IL-6 (p &lt; 0.001), and TNF-\u03b1 (p &lt; 0.001) levels in group D versus B, and lower IL-6 and TNF-\u03b1 in group D versus A (both p &lt; 0.001). Mesh culture positivity rate was higher in group B than A (p &lt; 0.001) and showed a non-significant reduction in group D versus B (p = 0.10). No perioperative deaths occurred. Conclusions: NAC attenuated septic, mesh-associated inflammation\u2014normalizing adhesions and histology and reducing IL-6 and TNF-\u03b1\u2014 supporting its role as a host-directed adjunct alongside antibiotics. Further translational studies are warranted to define the optimal dose, timing, and clinical indications.<\/jats:p>","DOI":"10.3390\/medsci13040318","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T10:11:23Z","timestamp":1765793483000},"page":"318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of N-Acetyl-L-Cysteine (NAC) on Inflammation After Intraperitoneal Mesh Placement in an Escherichia coli Septic Rat Model: A Randomized Experimental Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Styliani","family":"Parpoudi","sequence":"first","affiliation":[{"name":"Surgical Breast Oncology Department, Theageneio Hospital, 546 39 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Mantzoros","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-8783","authenticated-orcid":false,"given":"Orestis","family":"Ioannidis","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Zapsalis","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomai","family":"Gamali","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8139-3357","authenticated-orcid":false,"given":"Dimitrios","family":"Kyziridis","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Gekas","sequence":"additional","affiliation":[{"name":"Orthopaedic Department, Ippokrateio Hospital, 546 42 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5650-7319","authenticated-orcid":false,"given":"Elissavet","family":"Anestiadou","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savvas","family":"Symeonidis","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8281-1189","authenticated-orcid":false,"given":"Stefanos","family":"Bitsianis","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efstathios","family":"Kotidis","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manousos-Georgios","family":"Pramateftakis","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3562-7108","authenticated-orcid":false,"given":"Dimosthenis","family":"Miliaras","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Bikouli","sequence":"additional","affiliation":[{"name":"1st Intensive Care Unit, George Papanikolaou Hospital, 570 10 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0886-8017","authenticated-orcid":false,"given":"Georgios","family":"Iosifidis","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy, Histology & Embryology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stamatios","family":"Angelopoulos","sequence":"additional","affiliation":[{"name":"4th Department of Surgery, General Hospital \u201cGeorge Papanikolaou\u201d, Aristotle University of Thessaloniki, 570 10 Exochi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13017-017-0149-y","article-title":"2017 Update of the WSES Guidelines for Emergency Repair of 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