Hypoxic damage generates reactive oxygen species in isolated perfused rat liver.
The aim of the present study was to investigate the possible role of reactive oxygen species in the pathogenesis of hypoxic damage in isolated perfused rat liver. One hour of hypoxia caused severe cell damage (lactate dehydrogenase release of greater than 12,000 mU/min/g liver wt) and total irreversible cholestasis which was accompanied by a loss of cellular ATP and a marked decrease in lactate efflux. Tissue glutathione disulfide (GSSG) content and GSSG efflux as a measure of hepatic reactive oxygen formation was less than 1% of total glutathione before and during hypoxia. Upon reoxygenation, however, hepatic GSSG content increased sharply to about twice the control values and GSSG efflux increased several-fold to around 3-4 nmol GSH-equivalents/min/g. The release of lactate dehydrogenase decreased upon reoxygenation and tissue ATP content recovered partially. When livers were reoxygenated at an earlier time interval than 1 hr of hypoxia, i.e., before the onset of damage, no enhanced GSSG formation was observed. The results demonstrate that hypoxic damage is a prerequisite to reactive oxygen formation during the subsequent reoxygenation period. Thus, reactive oxygen species appear unlikely to play a crucial role in the pathogenesis of hypoxic liver damage in the hemoglobin-free, isolated perfused liver model.
Jaeschke
H
H
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Smith
C V
CV
Mitchell
J R
JR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism*; D019803:Glutathione Disulfide; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344
D007773:Lactates; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D019803:Glutathione Disulfide