Abstract | BACKGROUND & AIMS: METHODS: Livers of male Sprague-Dawley rats subjected to 24 hours of cold ischemia in University of Wisconsin solution (4 degrees C) were reperfused for 2 hours in the absence (controls) or presence of 0.5, 1, 2, or 4 mmol/L GSH (n = 4-6 each). RESULTS: Two hours after starting reperfusion of control livers, the sinusoidal release of lactate dehydrogenase and purine nucleoside phosphorylase increased to 247 +/- 96 and 27 +/- 13 mU. min(-1). g liver(-1), respectively, but only to 76 +/- 43 and 10 +/- 4 mU. min(-1). g liver(-1) in the presence of 4 mmol/L GSH. This cytoprotective effect was confirmed histologically by a marked reduction of trypan blue staining of hepatocytes. Compared with control livers, postischemic bile flow was significantly enhanced by GSH (0.15 +/- 0.02 vs. 0.41 +/- 0.11 microL. min(-1). g liver(-1)), indicating improved liver function. During reperfusion of control livers, intracellular GSH content declined from 4.5 +/- 0.3 to 2.3 +/- 0.1 micromol/g liver, but only to 3.8 +/- 0.4 micromol/g liver in the presence of 4 mmol/L GSH. Reperfusion of untreated livers was accompanied by a prolonged increase of portal pressure to maximally 12.5 +/- 1.9 cm H2O, which was significantly attenuated by 4 mmol/L GSH (7.2 +/- 1.4 cm H2O). Similar cytoprotective and hemodynamic effects were observed with 2 mmol/L GSH, but not with 0.5 and 1 mmol/L GSH. CONCLUSIONS: Treatment of cold-preserved livers with GSH upon reperfusion prevents damage of hepatocytes, deterioration of the hepatic circulation, and loss of intracellular GSH. In view of these protective effects and its low toxicity in humans, GSH should be considered a candidate drug for prevention of ROS-related reperfusion injury of the liver allograft.
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Authors | M Bilzer, G Paumgartner, A L Gerbes |
Journal | Gastroenterology
(Gastroenterology)
Vol. 117
Issue 1
Pg. 200-10
(Jul 1999)
ISSN: 0016-5085 [Print] United States |
PMID | 10381928
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- L-Lactate Dehydrogenase
- Purine-Nucleoside Phosphorylase
- Glutathione
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Topics |
- Animals
- Cryopreservation
- Glutathione
(metabolism, pharmacology)
- In Vitro Techniques
- Intracellular Membranes
(metabolism)
- Ischemia
(physiopathology)
- L-Lactate Dehydrogenase
(metabolism)
- Liver
(blood supply, drug effects, metabolism, pathology, physiopathology)
- Liver Circulation
(drug effects)
- Male
- Portal System
(physiopathology)
- Pressure
- Purine-Nucleoside Phosphorylase
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(prevention & control)
- Time Factors
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