Glutathione and ultrastructural changes in inflow occlusion of rat liver.

BACKGROUND

Liver ischemia/reperfusion is frequently associated with organ injury to which reactive oxygen species contribute. The aim of our study was to evaluate cytosolic and mitochondrial glutathione levels and morphological changes in hepatocytes of rat liver in an experimental model of ischemia/reperfusion.

MATERIALS AND METHODS

The experimental procedure consisted of temporary interruption of blood flow to the left lateral and medial hepatic lobes for different lengths of time and, in some cases, subsequent reperfusion. Cytosolic and mitochondrial glutathione levels were evaluated and ultrastructural analysis was carried out for all samples.

RESULTS

Ischemic lobes showed ultrastructural changes in relationship with the increase in ischemia time. Total glutathione levels did not show variations in ischemic lobes and sham lobes with respect to control rats during ischemia only. Instead, during reperfusion, significant ultrastructural alterations of the hepatocytes and a significant depletion of glutatione in cytosolic and mitochondrial compartments were evident. The sham lobes also showed a significant glutathione decrement. Increased oxidized glutathione (GSSG) levels were found during ischemia both in ischemic lobes and in sham lobes. During reperfusion GSSG was found to a minor extent, in the cytosolic compartment. In mitochondria GSSG levels were also high during reperfusion.

CONCLUSIONS

We conclude that depletion of glutathione contributes to impaired liver after reperfusion following ischemia but depletion of glutathione alone does not induce changes in the morphology of the hepatocytes. Glutathione depletion and a greater quantity of GSSG, even in sham lobes, may indicate a metabolic alteration which spreads to compartments that are not involved in ischemia/reperfusion.