90th Annual Meeting Abstracts
N-acetyl-L-cysteine (NAC) Reduces Intraabdominal Adhesion Formation Through The Upregulation Of Peritoneal Fibrinolytic Activity And Antioxidant Defenses
*Daniel I Chu, MD, *Rizal Lim, MD, *Stanley Heydrick, PhD, *Karen L Reed, PhD, *Arthur F Stucchi, PhD, James M Becker, MD
Boston University School of Medicine, Boston, MA
Introduction: Intraabdominal adhesions are a major source of morbidity and efforts to prevent them remain limited. Our laboratory has shown that adhesions are reduced by mechanisms that upregulate peritoneal fibrinolysis and antioxidant capacity. NAC is a clinically relevant antioxidant that increases intracellular glutathione levels. Its ability to reduce adhesions is unknown. We hypothesized that NAC would reduce adhesions and characterized its effects on peritoneal fibrinolysis and antioxidant defenses.
Methods: Abdominal adhesions were induced using our ischemic button model. Male Wistar rats (n = 40) were randomized to three groups: non-operative controls (NON-OP), operative controls (OP+Saline) or operative treatment with NAC (OP+NAC). Operated animals were administered either 1-cc normal saline (vehicle) or NAC (150mg/kg) intraperitoneally BID on pre-op day 1, operative day and post-op day 1. Animals were sacrificed at 7 days for adhesion scoring or at 24hrs to evaluate peritoneal fluid for fibrinolytic activity and tissue for tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) mRNA by RT-PCR, PAI-1 protein by Western blot and glutathione (GSH) and the oxidative stress marker, 8-isoprostane, by ELISA.
Results: NAC treatment reduced adhesions by 53% (p<0.001) and increased peritoneal fibrinolytic activity by 177% (p=0.002). Peritoneal tPA mRNA levels increased by nearly two-fold with NAC (p=0.007) while PAI-1 protein levels decreased by 30% (p=0.047). Surgery reduced peritoneal adhesion tissue GSH levels by 92% but NAC reconstituted GSH levels four-fold to 33% of NON-OP (p<0.001) and decreased the oxidative stress marker, 8-isoprostane, by 55% (p=0.013).
Conclusions: NAC administered intraperitoneally reduces adhesion formation while upregulating peritoneal fibrinolytic activity and antioxidant defenses. These data suggest a potentially new therapeutic use for NAC in adhesion prevention.