Basic Research
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 15, 2004; 10(6): 864-870
Published online Mar 15, 2004. doi: 10.3748/wjg.v10.i6.864
Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation
Rolf J. Schauer, Sinan Kalmuk, Alexander L. Gerbes, Rosemarie Leiderer, Herbert Meissner, Friedrich W. Schildberg, Konrad Messmer, Manfred Bilzer
Rolf J. Schauer, Sinan Kalmuk, Friedrich W. Schildberg, Surgical Department, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany
Alexander L. Gerbes, Manfred Bilzer, Department of Medicine II, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany
Rosemarie Leiderer, Konrad Messmer, Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany
Herbert Meissner, Institute of Pathology, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Rolf J. Schauer, Surgical Department, University Hospital Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany. schauer@gch.med.uni-muenchen.de
Telephone: +49-89-7095-3560 Fax: +49-89-7095-8894
Received: January 10, 2004
Revised: January 23, 2004
Accepted: February 28, 2004
Published online: March 15, 2004
Abstract

AIM: To investigated the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation.

METHODS: Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting. During a 2-h reperfusion period either saline (controls, n = 8) or GSH (50 or 100 μmol/(h·kg), n = 5 each) was continuously administered via the jugular vein.

RESULTS: Two hours after starting reperfusion plasma ALT increased to 1 457 ± 281 U/L (mean ± SE) in controls but to only 908 ± 187 U/L (P < 0.05) in animals treated with 100 μmol GSH/(h·kg). No protection was conveyed by 50 μmol GSH/(h·kg). Cytoprotection was confirmed by morphological findings on electron microscopy: GSH treatment prevented detachment of sinusoidal endothelial cells (SEC) as well as loss of microvilli and mitochondrial swelling of hepatocytes. Accordingly, postischemic bile flow increased 2-fold. Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules. Following infusion of 50 μmol and 100 μmol GSH/(h·kg), plasma GSH increased to 65 ± 7 mol/L and 97 ± 18 mol/L, but to only 20 ± 3 mol/L in untreated recipients. Furthermore, plasma glutathione disulfide (GSSG) increased to 7.5 ± 1.0 mol/L in animals treated with 100 μmol/(h·kg) GSH but did not raise levels of untreated controls (1.8 ± 0.5 mol/L) following infusion of 50 μmol GSH/(h·kg) (2.2 ± 0.2 mol/L).

CONCLUSION: Plasma GSH levels above a critical level may act as a “sink” for ROS produced in the hepatic vasculature during reperfusion of liver grafts. Therefore, GSH can be considered a candidate antioxidant for the prevention of reperfusion injury after liver transplantation, in particular since it has a low toxicity in humans.

Keywords: $[Keywords]