N-acetylcysteine failed to improve early microcirculatory alterations of the rat liver after transplantation.
The application of radical scavengers reduces reperfusion injury of liver grafts despite the natural occurrence of cellular defense mechanisms enabling the cell to tolerate moderate oxidant stress without further cell damage. The glutathione peroxidase mechanism of the liver serves to reduce hydroxyl radical-induced lipid peroxidation by releasing reduced glutathione from intracellular stores. There is evidence that the application of cysteine-providing amino acids for glutathione synthesis could maintain or even increase liver glutathione. Therefore, the purpose of this study was to evaluate the effect of N-acetylcysteine (NAC) on oxidative stress-induced reperfusion injury after liver transplantation. This was done by applying intravital microscopy. Livers from female Sprague-Dawley rats weighing 220-260 g were stored for 20 h in University of Wisconsin (UW) solution and transplanted orthotopically using the cuff technique. Donors were given 150 mg/kg body weight NAC i.v. or placebo in a blind, random fashion 6 h prior to harvesting, followed by two injections of 50 mg/kg body weight, 4 and 2 h before explantation. In additional experimental groups, recipients were given a bolus of 83 mg/kg body weight NAC or placebo at the beginning of the recipient operations, 1 min prior to reperfusion, and 60 min after surgery. Ninety minutes after transplantation, intravital microscopy was applied and five liver lobules were recorded for 30 s after injection of acridine orange, a fluorescent leukocyte marker. Sinusoidal perfusion, sinusoidal width, and leukocyte adhesion, as well as reduced and oxidized glutathione, were determined in all livers.(ABSTRACT TRUNCATED AT 250 WORDS)
Walcher
F
F
Clinic for Anesthesiology and Intensive Care Medicine, University of Saarland, Homburg/Saar, Germany.
Marzi
I
I
Flecks
U
U
Larsen
R
R
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism; D019803:Glutathione Disulfide; D007962:Leukocytes / Q000166:cytology; D008099:Liver / Q000098:blood supply*; D016031:Liver Transplantation / Q000502:physiology*; D008833:Microcirculation / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D005978:Glutathione; D019803:Glutathione Disulfide; D000111:Acetylcysteine