N-Acetylcysteine ameliorates the late phase of liver ischaemia/reperfusion injury in the rabbit with hepatic steatosis.
Steatotic livers are highly susceptible to I/R (ischaemia/reperfusion) injury and, therefore, the aim of the present study was to evaluate the in vivo effect of NAC (N-acetylcysteine) on hepatic function in the early and initial late phase of warm liver I/R injury in steatotic rabbits. Twelve New Zealand White rabbits were fed a high-cholesterol (2%) diet. The control group (n=6) underwent lobar liver ischaemia for 1 h, followed by 6 h of reperfusion. In the treated group receiving NAC (n=6), an intravenous infusion of NAC was administered prior to and during the 6 h reperfusion period. Systemic and hepatic haemodynamics were monitored continuously. ALT (alanine aminotransferase) activity and bile production were measured. NMR spectroscopy was used to analyse bile composition. Oxidation of DHR (dihydrorhodamine) to RH (rhodamine) was used as a marker of production of reactive oxygen and nitrogen species. Moderate centrilobular hepatic steatosis was demonstrated by histology. The results showed that NAC administration significantly improved portal flow, hepatic microcirculation, bile composition and bile flow after 5 h of reperfusion. NAC administration was also associated with less hepatocellular injury, as indicated by ALT serum activity, and decreased the oxidation of DHR to RH. In conclusion, NAC administration decreased the extent of I/R injury in the steatotic liver, particularly during the late phase of reperfusion.
University Department of Surgery and Liver Transplant Unit, Royal Free Hospital, Royal Free and University College Medical School, Pond Street, London NW3 2QG, U.K.
Giuseppe
G
Fusai
George K
GK
Glantzounis
Tarek
T
Hafez
Wenxuan
W
Yang
Alberto
A
Quaglia
Hemant
H
Sheth
Sanjeev
S
Kanoria
Harry
H
Parkes
Alexander
A
Seifalian
Brian R
BR
Davidson
D000111:Acetylcysteine / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005234:Fatty Liver / Q000150:complications* / Q000209:etiology / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008833:Microcirculation / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
D002791:Cholesterol, Dietary; D000410:Alanine Transaminase; D000111:Acetylcysteine