Reoxygenation injury of rat hepatocytes: evaluation of nucleotide depletion and oxidative stress as causal components.
Isolated rat hepatocytes were used for the evaluation of nucleotide depletion and oxidative stress as two causal components of postischemic injury following oxygen deficiency. The ATP and GTP loss during anoxia was accompanied by temporary increases of nucleotide degradation products. The critical duration of anoxia for a complete ATP restoration during reoxygenation was between 30 and 60 min. The oxidative stress during reoxygenation was demonstrated by decrease of GSH concentration and increase of TBA-RS level. The tremendous GSH loss could not be balanced by the slight GSSG increase during reoxygenation. Prevention of GSH decrease and TBA-RS increase in parallel to prevention of viability loss in presence of oxipurinol in contrast to lacking improvement of ATP and GTP restoration by this drug speak in favor for the oxidative stress as major causal component for postischemic injury of hepatocytes in comparison with depletion of energy-rich purine nucleotides. The inhibition of formation of reactive oxygen species via xanthine oxidase reactions was found to be the dominant protective effect of oxipurinol against postischemic injury of hepatocytes in comparison with lacking influence on nucleotide salvage and ATP/GTP regeneration and with radical scavenging.
Grune
T
T
Klinik für Physikalische Medizin und Rehabilitation, Humboldt Universität zu Berlin, Federal Republic of Germany.
Schneider
W
W
Siems
W G
WG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D004734:Energy Metabolism; D005978:Glutathione / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008297:Male; D009711:Nucleotides / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology*; D010101:Oxygen Consumption; D010117:Oxypurinol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D013312:Stress, Physiological / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D009711:Nucleotides; D017392:Thiobarbituric Acid Reactive Substances; D000493:Allopurinol; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D010117:Oxypurinol; D005978:Glutathione; D010100:Oxygen