Efficacy of preconditioning with N-acetylcysteine against reperfusion injury after prolonged cold ischaemia in rats liver in which glutathione had been reduced by buthionine sulphoximine.
OBJECTIVE
To investigate the ability of N-acetylcysteine (NAC) to prevent cold ischaemic-reperfusion injury and improve hepatic integrity in a glutathione-depleted condition.


METHODS
Open laboratory study.


METHODS
University hospitals, Japan and France.


METHODS
40 male Wistar rats.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Nagasaki
H
H
Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan.
Nakano
H
H
Boudjema
K
K
Jaeck
D
D
Alexandre
E
E
Baek
Y
Y
Kitamura
N
N
Yamaguchi
M
M
Kumada
K
K
D000111:Acetylcysteine / Q000627:therapeutic use*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D003080:Cold Temperature; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D019328:Buthionine Sulfoximine; D000255:Adenosine Triphosphate; D005978:Glutathione; D000111:Acetylcysteine