N-acetyl-l-cysteine decreases intra-abdominal adhesion formation through the upregulation of peritoneal fibrinolytic activity and antioxidant defenses
| Autor: | Daniel I. Chu, Stanley Heydrick, Arthur F. Stucchi, Rami Abdou, Melanie L. Gainsbury, Karen L. Reed, James M. Becker, Rizal Lim, Laura D’Addese |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_treatment Adhesion (medicine) Tissue Adhesions Pharmacology Dinoprost medicine.disease_cause Tissue plasminogen activator Antioxidants Abdomen Plasminogen Activator Inhibitor 1 Fibrinolysis medicine Animals Humans Rats Wistar Saline Cells Cultured Wound Healing Dose-Response Relationship Drug business.industry Epithelial Cells medicine.disease Glutathione Acetylcysteine Rats Up-Regulation Oxidative Stress Dose–response relationship Tissue Plasminogen Activator Models Animal Immunology Surgery Peritoneum business Wound healing Plasminogen activator Injections Intraperitoneal Oxidative stress medicine.drug |
| Zdroj: | Surgery. 149:801-812 |
| ISSN: | 0039-6060 |
| DOI: | 10.1016/j.surg.2011.02.015 |
| Popis: | Intraperitoneal adhesions occur in more than 94% of patients after abdominal surgery. Mechanisms that decrease oxidative stress and upregulate peritoneal fibrinolysis reduce adhesions. N-acetyl-l-cysteine (NAC) is a clinically relevant antioxidant whose effect on peritoneal fibrinolysis and ability to decrease adhesions has not been established. The aims of this study were to determine if NAC reduces adhesions and to characterize its potential mechanism(s) of action.Male Wistar rats (n = 92) received 0.9% saline (OP Control), intraperitoneal NAC (150 mg/kg, OP + NAC), or oral NAC (1200 mg/kg) twice daily on preoperative day 1, day of operation, and postoperative day 1. Adhesions were induced on the day of operation using our previously described ischemic button model. Animals were killed on postoperative day 7 for adhesion scoring. Peritoneal tissue and fluid from the intraperitoneal NAC group were measured at 24 hours for fibrinolytic activity, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), total glutathione, and 8-isoprostane (8-IP). The effect of NAC on tPA and PAI-1 production was tested in vitro in human mesothelial cells. The effect of NAC on intestinal wound healing was measured using colonic anastomotic burst pressures.Intraperitoneal NAC reduced adhesions by 53% (P.001) compared to OP Controls without affecting anastomotic wound healing. NAC increased the tPA/PAI-1 protein ratio and peritoneal fibrinolytic activity by 69% and 127%, respectively, compared to OP Controls (P.05). NAC did not restore total glutathione levels in peritoneal adhesion tissue but decreased 8-IP by 46% and 65% (P.05) in peritoneal tissue and fluid, respectively, compared to OP Controls. Human mesothelial cells incubated with NAC exhibited a concentration-dependent increase in the tPA/PAI-1 ratio, which supported in vivo observations (P.05). Oral NAC did not decrease adhesions.NAC administered intraperitoneally decreased adhesion formation while upregulating peritoneal fibrinolytic activity and antioxidant defenses without affecting normal anastomotic wound healing. These data suggest a potential new therapeutic use for NAC in adhesion prevention. |
| Databáze: | OpenAIRE |
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