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.

Abstract

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: H Nagasaki, H Nakano, K Boudjema, D Jaeck, E Alexandre, Y Baek, N Kitamura, M Yamaguchi, K Kumada
• Journal: The European journal of surgery = Acta chirurgica (Eur J Surg) Vol. 164 Issue 2 Pg. 139-46 (Feb 1998) ISSN: 1102-4151 [Print] England
• PMID: 9537722 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Free Radical Scavengers
• Buthionine Sulfoximine
• Adenosine Triphosphate
• Glutathione
• Acetylcysteine

Topics

• Acetylcysteine (therapeutic use)
• Adenosine Triphosphate (biosynthesis)
• Animals
• Buthionine Sulfoximine (pharmacology)
• Cold Temperature
• Enzyme Inhibitors (pharmacology)
• Free Radical Scavengers (therapeutic use)
• Glutathione (metabolism)
• In Vitro Techniques
• Ischemic Preconditioning (methods)
• Liver (blood supply, enzymology, metabolism)
• Male
• Oxidation-Reduction
• Rats
• Rats, Wistar
• Reperfusion Injury (prevention & control)