MECHANISM AND PREVENTION OF ISCHEMIA REPERFUSION-INDUCED LIVER-INJURY IN RATS

This study was designed to clarify the mechanism of ischemia-reperfusion-induced rat liver injury and to evaluate the effect of long-acting superoxide dismutase (SOD-POE). Liver mitochondrial functional indices, i.e., the respiratory control index (RCI) and the rate of oxygen consumption in State III respiration (St. III O2), were decreased significantly to 1.33 ± 0.06, means ± SD, and 54.4 ± 3.7 natom/mg protein/min, respectively, after 120 min of ischemia, compared to respective preischemic values (3.94 ± 0.21 and 80.2 ± 3.9). These indices did not recover fully following 60 min of reperfusion (RCI, 3.25 ± 0.17; St. III O2, 69.9 ± 6.4). Tissue levels of adenosine triphosphate (ATP) were decreased to 2% of preischemic levels after 120 min of ischemia and remained at 39% of preischemic levels following 60 min of reperfusion. Increases in hypoxanthine and xanthine were observed after ischemia. SOD-POE improved the recovery of mitochondrial function (RCI, 3.70 ± 0.20; St. III O2, 83.3 ± 7.6) and also accelerated the recovery of ATP (53% of preischemic level). SOD-POE did not affect the decrease in ATP levels or the increase in purine nucleotide levels during ischemia. SOD-POE did not influence changes in tissue blood flow levels throughout the experiments. The leakage of adenine nucleotides immediately after reperfusion was observed (4.2 ± 2.0 μmole/liter serum), and SOD-POE mitigated this leakage (1.3 ± 0.5). Purine nucleotides are oxidizable substrates of xanthine oxidase, and an increase in superoxide radical generation by this enzyme might be expected in the ischemia-reperfusion process. Accordingly, these results suggest that superoxide radical is a major contributory factor to postischemic liver injury, and the clinical application of SOD-POE might be expected. © 1991.