OBJECTIVE: To investigate the ability of N-acetylcysteine (NAC) to prevent cold ischaemic-reperfusion injury and improve hepatic integrity in a glutathione-depleted condition. DESIGN: Open laboratory study. SETTING: University hospitals, Japan and France. MATERIALS: 40 male Wistar rats. INTERVENTIONS: To produce a glutathione-depleted liver, buthionine sulphoximine (BSO) was injected intraperitoneally 2 hours before either NAC or 5% dextrose was infused 15 minutes before the liver was harvested. We used an isolated perfused rat liver model that had undergone prolonged hypothermic ischaemia, cold-storage for 48 hours and reperfusion for 120 minutes. MAIN OUTCOME MEASURES: Concentrations of hepatic enzymes released into samples of perfusate, concentration of adenosine triphosphate in liver tissue, concentrations of reduced and oxidized glutathione in perfusate, and bile production. RESULTS: The concentrations of the hepatocellular enzymes and oxidised glutathione in the perfusate samples were significantly reduced in the NAC group compared with the 5% dextrose group. Bile production improved significantly in the NAC group compared with the 5% dextrose group. The concentration of reduced glutathione in liver tissue was not increased by NAC. CONCLUSION: In a glutathione-depleted liver NAC prevented hepatic injury and improved liver integrity after a cold ischaemic-reperfusion injury, by acting not as a substrate for glutathione synthesis but as a direct free radical scavenger.
OBJECTIVE: To investigate the ability of N-acetylcysteine (NAC) to prevent cold ischaemic-reperfusion injury and improve hepatic integrity in a glutathione-depleted condition. DESIGN: Open laboratory study. SETTING: University hospitals, Japan and France. MATERIALS: 40 male Wistar rats. INTERVENTIONS: To produce a glutathione-depleted liver, buthionine sulphoximine (BSO) was injected intraperitoneally 2 hours before either NAC or 5% dextrose was infused 15 minutes before the liver was harvested. We used an isolated perfused rat liver model that had undergone prolonged hypothermic ischaemia, cold-storage for 48 hours and reperfusion for 120 minutes. MAIN OUTCOME MEASURES: Concentrations of hepatic enzymes released into samples of perfusate, concentration of adenosine triphosphate in liver tissue, concentrations of reduced and oxidized glutathione in perfusate, and bile production. RESULTS: The concentrations of the hepatocellular enzymes and oxidised glutathione in the perfusate samples were significantly reduced in the NAC group compared with the 5% dextrose group. Bile production improved significantly in the NAC group compared with the 5% dextrose group. The concentration of reduced glutathione in liver tissue was not increased by NAC. CONCLUSION: In a glutathione-depleted liver NAC prevented hepatic injury and improved liver integrity after a cold ischaemic-reperfusion injury, by acting not as a substrate for glutathione synthesis but as a direct free radical scavenger.
Authors: Mohammed Reza Moussavian; Claudia Scheuer; Michael Schmidt; Otto Kollmar; Matthias Wagner; Maximilian von Heesen; Martin K Schilling; Michael D Menger Journal: Langenbecks Arch Surg Date: 2010-06-27 Impact factor: 3.445
Authors: Farin Amersi; Sally K Nelson; Xiu Da Shen; Hirohisa Kato; Judy Melinek; Jerzy W Kupiec-Weglinski; Lawrence D Horwitz; Ronald W Busuttil; Marcus A Horwitz Journal: Proc Natl Acad Sci U S A Date: 2002-06-25 Impact factor: 11.205
Authors: Mariapia Vairetti; Laura Giuseppina Di Pasqua; Marta Cagna; Plinio Richelmi; Andrea Ferrigno; Clarissa Berardo Journal: Antioxidants (Basel) Date: 2021-02-28