The
glutathione in mitochondria is thought to play a crucial role in protecting mitochondria against
ischemia-reperfusion-induced injury. However, little is known about the mitochondrial redox system. This study was conducted to clarify changes of mitochondrial
glutathione redox during liver
ischemia and reperfusion and its role on energy producing function. Rats were divided into three groups each of which were treated respectively with saline (Control),
buthionine sulfoximine (BSO), which induces a rapid decrease in tissue
glutathione concentrations, and
gamma-glutamylcysteine ethyl
ester (GCE), which conversely induces a rapid increase in tissue
glutathione concentrations before induction of
ischemia. Liver
ischemia was induced for 120 min, and blood reflow was subsequently restored for 60 min. Total and mitochondrial
glutathione concentrations, mitochondrial respiratory function, and tissue
adenine nucleotide were determined after both the ischemic and the reperfusion periods. In all groups, concentrations of the reduced form of
glutathione (GSH) gradually decreased during
ischemia and reperfusion. On the other hand, significant increases in mitochondrial GSH were apparent after reperfusion despite significant decreases during
ischemia in the control and GCE groups. Total and mitochondrial GSH in the BSO and GCE groups were significantly lower and higher, respectively, compared with the control throughout the experiment. Recovery of the mitochondrial energy producing function and cellular
adenine nucleotide after reperfusion were dependent on GSH concentrations. We conclude that mitochondrial GSH concentrations dramatically change in a different manner from cytosolic concentrations after reperfusion, and that recovery of the mitochondrial energy-producing function might be closely associated with mitochondrial GSH concentrations.