Changes of mitochondrial respiratory functions and superoxide dismutase activity during liver regeneration

The general objective of this study was to examine the relationship between mitochondrial respiratory function and liver regeneration in the rat. The role that free radicals may play in the process was also evaluated. It was found that the respiratory control and ADP/O ratios were concomitantly decreased to the lowest level at 6 hr after hepatectomy and gradually recovered thereafter. Both ratios were significantly increased at 48 hr and quickly reached plateau levels. Assays of mitochondrial respiratory functions revealed that the activities of Complex I+III, Complex II+III and Complex IV all decreased drastically at 6 hr after hepatectomy and then gradually returned to the original level during 18-24 hr after hepatectomy. Interestingly, the activities of all these enzyme complexes continuously increased and were elevated significantly above the normal levels (145-200%). In contrast, the liver mitochondrial electron transport activities of sham-operated rats returned only to the original level after recovering from the operation-induced decline at 6 hr post-hepatectomy. We measured the superoxide dismutase (SOD) activity of liver mitochondria of the hepatectomized and sham-operated rats. The results showed that the Mn-SOD activity started to increase after hepatectomy, reached a maximum (900% of control) at 6 hr, and then returned to normal levels at 24 hr after operation. The Cu, Zn-SOD activity was increased 9-fold in hepatectomized rats and about 3-fold in sham-operated rats as compared with control rats. The maximum activity of Mn-SOD was found to be about 4 times higher than that of Cu, Zn-SOD after hepatectomy. The amount of lipoperoxides in the liver mitochondria was found to be increased to 140% in hepatectomized rats and to 120% in sham-operated rats as compared with that of the control rats. Taken together these results suggest that the changes in mitochondrial respiratory functions in the early phase of hepatectomy are due to tissue damage caused by the transient elevation of free radicals. These free radicals are then quickly disposed of by the ever-increasing activities of the Mn-SOD and Cu, Zn-SOD in the liver mitochondria, thereby protecting the liver from further damage and gearing the organ to the regeneration process.