The influence of selenium substitution on microcirculation and glutathione metabolism after warm liver ischemia/reperfusion in a rat model

Ischemia/reperfusion (I/R) injury is a variable yet unavoidable complication in liver surgery and transplantation. Selenium-dependent glutathione-peroxidases (GPx) and selenoproteins function as antioxidant defense systems. One target in preventing I/R injury is enhancing the capacity of endogenous redox defense. It was the aim of this study to analyze the effects of selenium substitution on liver microcirculation, hepatocellular injury and glutathione status in a model of partial warm liver ischemia in the rat. Sodium selenite was administered in three different dosages i.v.: 0.125 mu g/g, 0.25 mu g/g and 0.375 mu g/g body weight and compared to an untreated control group (each n = 10). Intravital microscopy was performed after 70 min of partial warm liver ischemia and 90 min of reperfusion. Liver tissue and plasma samples were taken at the end of the experiment for laboratory analysis. Microcirculation improved significantly in all therapy groups in contrast to control animals. ALT levels decreased significantly whereas malondialdehyde levels remained unchanged. In liver tissue, selenium supplementation caused an increase in the amount of total and reduced glutathione without changes in oxidized glutathione. This effect is likely mediated by selenite itself and selenoprotein P rather than by modulating GPx activity. We were able to show that selenite substitution has an immediate protective effect on I/R injury after warm hepatic ischemia by acting as a radical scavenger and preserving the antioxidative capacity of the liver. (C) 2008 Elsevier Inc. All rights reserved.