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, mean +/- 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 mumole/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Kobayashi
H
H
Department of Surgery II, Faculty of Medicine, University of Nagoya, Japan.
Nonami
T
T
Kurokawa
T
T
Sugiyama
S
S
Ozawa
T
T
Takagi
H
H
D000227:Adenine Nucleotides / Q000097:blood / Q000378:metabolism; D000818:Animals; D006503:Hepatic Veins; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007511:Ischemia / Q000150:complications*; D008102:Liver Circulation; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000517:prevention & control*; D019820:Xanthine; D014970:Xanthines / Q000378:metabolism
D000227:Adenine Nucleotides; D007042:Hypoxanthines; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine