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N-Acetylcysteine failed to improve early microcirculatory alterations of the rat liver after transplantation
- Source :
- Transplant International. 8:317-323
- Publication Year :
- 1995
- Publisher :
- Frontiers Media SA, 1995.
-
Abstract
- 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 aminoacids 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. Neither microcirculatory disturbance nor leukocyte adhesion was less, nor was the liver glutathione in the recipient groups pretreated or treated with NAC greater than that in rats receiving the placebo. Moreover, liver glutathione was significantly decreased in livers from donors pretreated with NAC. In conclusion, the application of NAC as a pretreatment for donors and as treatment for recipients, respectively, failed to reduce early microvascular failure after liver transplantation.
- Subjects :
- Pathology
medicine.medical_specialty
medicine.medical_treatment
Pharmacology
Liver transplantation
Rats, Sprague-Dawley
Acetylcysteine
Random Allocation
chemistry.chemical_compound
Cell Adhesion
Leukocytes
medicine
Animals
Lobules of liver
Liver preservation
chemistry.chemical_classification
Transplantation
Glutathione Disulfide
business.industry
Microcirculation
Glutathione peroxidase
Glutathione
Liver Transplantation
Rats
Liver
chemistry
Reperfusion Injury
Glutathione disulfide
Female
business
Intravital microscopy
medicine.drug
Subjects
Details
- ISSN :
- 14322277 and 09340874
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Transplant International
- Accession number :
- edsair.doi.dedup.....46dc3f84da4ddcdd686ed72926056df5