EFFICACY OF PRECONDITIONING WITH N-ACETYLCYSTEINE AGAINST REPERFUSIONINJURY AFTER PROLONGED COLD ISCHEMIA IN RATS LIVER IN WHICH GLUTATHIONE HAD BEEN REDUCED BY BUTHIONINE SULFOXIMINE

Objective: To investigate the ability of N-acetylcysteine (NAC) to pre vent cold ischaemic-reperfusion injury and improve hepatic integrity i n a glutathione-depleted condition. Design: Open laboratory study. Set ting: University hospitals, Japan and France. Materials: 40 male Wista r rats. Interventions: To produce a glutathione-depleted liver, buthio nine 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 under gone prolonged hypothermic ischaemia, cold storage for 48 hours and re perfusion for 120 minutes. Main outcome measures: Concentrations of he patic enzymes released into samples of perfusate, concentration of ade nosine triphosphate in liver tissue, concentrations of reduced and oxi dized glutathione in perfusate, and bile production. Results; The conc entrations of the hepatocellular enzymes and oxidised glutathione in t he perfusate samples were significantly reduced in the NAC group compa red with the 5% dextrose group. Bile production improved significantly in the NAC group compared with the 5% dextrose group. The concentrati on of reduced glutathione in liver tissue was not increased by NAC. Co nclusion: In a glutathione-depleted liver NAC prevented hepatic injury and improved liver integrity after a cold ischaemic-reperfusion injur y, by acting not as a substrate for glutathione synthesis but as a dir ect free radical scavenger.