Original CommunicationN-acetyl-l-cysteine decreases intra-abdominal adhesion formation through the upregulation of peritoneal fibrinolytic activity and antioxidant defenses
Section snippets
Materials
NAC was obtained from Sigma (catalog no. A7250; St. Louis, MO) and prepared in 0.9% “normal” saline at the stated concentrations.
Animals
Male Wistar rats (range, 200–225 g; Charles River Laboratories, Wilmington, MA) were housed at constant room temperature and under 12-hour light/12-hour dark cycles and allowed access to food and water ad libitum. The Institutional Animal Care and Use Committee at the Boston University School of Medicine approved this study, and all procedures described were performed
Intraperitoneal NAC inhibits adhesion formation
NAC administered intraperitoneally at twice-a-day dosing on preoperative day 1, operative day, and postoperative day 1 (OP + NAC) decreased intraabdominal adhesions by 53% compared to OP Controls (P < .001) (Fig 2, A). In a series of experiments to optimize intraperitoneal NAC dosing by removing pre- or postoperative doses (Table), we were unable to show any decreases in adhesions if we decreased the number of doses. Similarly, increasing a 1-time intraoperative dose of NAC to 300 mg/kg was
Discussion
The data presented here show that NAC administered intraperitoneally, but not orally, decreases intraabdominal adhesions while upregulating peritoneal fibrinolytic activity and antioxidant capacity, with no effect on anastomotic wound healing. NAC is used in a variety of clinical settings but its intraperitoneal administration in adhesion prevention has, to our knowledge, never been studied.
Given its potent antioxidant properties and the mounting evidence that antioxidants decrease adhesions,
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2023, Journal of Drug Delivery Science and TechnologyEffect of N-acetyl-L-cysteine on inflammation after intraperitoneal mesh placement in a potentially contaminated environment: An experimental study in the rat
2022, Asian Journal of SurgeryCitation Excerpt :Relevant to our study design, we chose to administer NAC as a single dose in order to accord with a feasible clinical application. In view of collecting more data we set the interval for follow up at 21 days after intervention contrary to a study period of 7 days published by Chu et al.32 In conclusion, our results support the hypothesis that the introduction of NAC intraperitoneally results in a significant decrease in inflammatory reaction and in adhesion formation due to its known anti-inflammatory and fibrinolytic properties.
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2022, Clinica Chimica ActaCitation Excerpt :Experimental peritoneal oxidative stress in rats acutely damaged the mesothelium and chronically resulted in fibrosis and bowel ligatures [60]. Increased fibrinolysis in a rat adhesion model was observed upon intraperitoneal administration of the antioxidant, N-acetyl-L-cysteine; however, glutathione levels were not restored [63]. The amino acid central to combating oxidative stress, L-cysteine, was decreased, whereas the oxidized form, L-cystine, was increased in SBO rA compared to appy rA.
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2022, Journal of Surgical ResearchIntra-abdominal adhesions: Anatomy, physiology, pathophysiology, and treatment
2015, Current Problems in SurgeryCombined intraoperative administration of a histone deacetylase inhibitor and a neurokinin-1 receptor antagonist synergistically reduces intra-abdominal adhesion formation in a rat model
2015, Surgery (United States)Citation Excerpt :Numerous studies have firmly established that peritoneal fibrinolysis is compromised after surgery, either by a reduction in tPA or an increase in its principal inhibitor, plasminogen activator inhibitor-1,34 or both, indicating that peritoneal fibrin accumulation and stabilization is a key underlying event early in adhesiogenesis.18,31,32,35 Although our previous studies showed that augmenting the peritoneal fibrinolytic system reduced adhesion formation in a rat model,14-16,19 the coadministration of any of these compounds did not increase adhesion prevention, owing in part, to their mechanistic similarities. When we discovered that VPA did not reduce adhesion formation via the fibrinolytic pathway,20 but instead by an alternative mechanism that limited the availability of fibrin substrates, we recognized a potential opportunity to achieve synergistic adhesion reduction by targeting both fibrinolysis with the NK-1RA and fibrin accumulation with VPA (Fig 5, B).
Supported in part by research grants from the Smithwick Endowment Fund, Department of Surgery, Boston University School of Medicine, and the Robert and Dana Smith Family Foundation.
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A.F.S. and J.M.B. contributed equally to this publication as senior authors.