N-Acetyl-L-Cysteine for reducing inflammation after surgery in rats?

Abstract

<b>Background/Objectives</b>: 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 <i>Escherichia coli</i> (<i>E.coli</i>) inoculation. The primary comparison was prospectively defined between <i>E. coli</i>-inoculated animals treated with NAC (D) and those without NAC (B). Groups without <i>E. coli</i> (A,C,E) are presented for context and were compared previously. <b>Methods</b>: In this randomized, double-blind experimental model (five groups, <i>n</i> = 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 <i>E. coli</i>, while the NAC-treated groups additionally received intraperitoneal NAC (150 mg/kg). Serum levels of IL-1α, IL-6, and TNF-α 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 χ² or Fisher's exact tests with Bonferroni-adjusted pairwise comparisons. <b>Results</b>: <i>E. coli</i> inoculation significantly increased adhesion burden and worsened histologic scores compared with controls (both <i>p</i> < 0.001). NAC administration in the septic model significantly reduced adhesions and improved all histologic domains relative to <i>E. coli</i> alone (all <i>p</i> ≤ 0.003), with values comparable to controls (non-significant across domains). For cytokines, there was a significant overall group effect for IL-1α, IL-6, and TNF-α (all <i>p</i> < 0.001), without a main effect of time or time × group interaction. Pairwise contrasts showed lower IL-1α (<i>p</i> = 0.024), IL-6 (<i>p</i> < 0.001), and TNF-α (<i>p</i> < 0.001) levels in group D versus B, and lower IL-6 and TNF-α in group D versus A (both <i>p</i> < 0.001). Mesh culture positivity rate was higher in group B than A (<i>p</i> < 0.001) and showed a non-significant reduction in group D versus B (<i>p</i> = 0.10). No perioperative deaths occurred. <b>Conclusions</b>: NAC attenuated septic, mesh-associated inflammation-normalizing adhesions and histology and reducing IL-6 and TNF-α- supporting its role as a host-directed adjunct alongside antibiotics. Further translational studies are warranted to define the optimal dose, timing, and clinical indications.