Mitochondria and xanthine oxidase both generate reactive oxygen species in isolated perfused rat liver after hypoxic injury.
Hypoxia caused severe damage in isolated perfused livers from fasted male Fischer rats without evidence of the formation of reactive oxygen species during hypoxia. Reoxygenation caused a significant increase in intracellular oxygen species in the injured liver, as indicated by increases in sinusoidal GSSG efflux and tissue GSSG levels. Both parameters were elevated further by addition of KCN (100 microM) or antimycin A (8 microM). Sinusoidal GSSG efflux was suppressed in part by addition of allopurinol (500 microM) and enhanced by hypoxanthine (250 microM). Xanthine oxidase appears to be a partial source, and damaged mitochondria a continuous and quantitatively greater source, of reactive oxygen as a result of liver injury following hypoxia.
Jaeschke
H
H
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Mitchell
J R
JR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001646:Bile / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*
D007042:Hypoxanthines; D013481:Superoxides; D019271:Hypoxanthine; D000493:Allopurinol; D000968:Antimycin A; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D014969:Xanthine Oxidase; D005978:Glutathione; D011190:Potassium Cyanide; D010100:Oxygen; D000640:Amitrole