Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver.

Abstract

We investigated whether intraportal injection of 150 mg/kg N-acetylcysteine (NAC) into rats reduced hepatic ischemia-reperfusion injury after 48 hours of cold storage and 2 hours of reperfusion. The organ was isolated and perfused to evaluate liver function. The control group received an intraportal injection of 5% dextrose. NAC increased L-cysteine concentrations 15 minutes after injection (1.29 +/- 0.11 mumol/g vs. 2.68 +/- 0.4 mumol/g, P < .05). However, neither treatment modified glutathione liver concentrations relative to preinjection values. After 48 hours of cold storage and 2 hours of reperfusion, livers from NAC-treated rats produced larger amounts of bile than those in the control group (5.04 +/- 1.92 vs. 0.72 +/- 0.37 microL/g liver; P < .05), and showed a significant reduction in liver injury, as indicated by reduced release of lactate dehydrogenase (679.4 +/- 174.4 vs. 1891.3 +/- 268.3 IU/L/g; P < .01), aspartate transaminase (AST) (13.94 +/- 3.5 vs. 38.75 IU/L/g; P < .01), alanine transaminase ALT) (14.92 +/- 4.09 vs. 45.91 +/- 10.58 IU/L/g; P < .05), and acid phosphatase, a marker of Kupffer cell injury (344.4 +/- 89.6 vs. 927.3 +/- 150.8 IU/L/g; P < .01) in the perfusate. Reduced glutathione concentrations in the perfusate were similar in the two groups (805 +/- 69 vs. 798 +/- 252 nmol/L/g), whereas oxidized glutathione (GSSG) concentrations were higher in the control group (967 +/- 137 vs. 525 +/- 126 nmol/L/g; P < .05). Reduced glutathione (GSH) concentrations in liver tissue collected at the end of perfusion were significantly higher in the NAC group (7.3 +/- 0.9 vs. 4.1 +/- 1.0 mumol/g; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: H Nakano, K Boudjema, E Alexandre, P Imbs, M P Chenard, P Wolf, J Cinqualbre, D Jaeck
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 22 Issue 2 Pg. 539-45 (Aug 1995) ISSN: 0270-9139 [Print] United States
• PMID: 7635422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Methionine Sulfoximine
• Buthionine Sulfoximine
• L-Lactate Dehydrogenase
• Aspartate Aminotransferases
• Alanine Transaminase
• Acid Phosphatase
• Glutathione
• Cysteine
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage, therapeutic use)
• Acid Phosphatase (metabolism)
• Alanine Transaminase (metabolism)
• Animals
• Aspartate Aminotransferases (metabolism)
• Buthionine Sulfoximine
• Cold Temperature
• Cysteine (metabolism)
• Glutathione (metabolism)
• L-Lactate Dehydrogenase (metabolism)
• Liver (blood supply, metabolism)
• Male
• Methionine Sulfoximine (analogs & derivatives, pharmacology)
• Oxidation-Reduction
• Rats
• Rats, Wistar
• Reperfusion Injury (prevention & control)