title: Hypoxic liver cell death: critical Po2 and dependence of viability on glycolysis.
abstract: Viability of isolated hepatocytes was not significantly dependent on oxygen at oxygen partial pressures (Po2) from 70 to 0.3 mmHg. The critical Po2 for induction of hypoxic cell death was close to 0.1 mmHg and was distinct from the value at which mitochondrial function becomes impaired (2-5 mmHg). Hypoxic damage in hepatocytes from fasted rats occurred within 1 h but was delayed by the addition of fructose, which increased rates of lactate formation from about 1 to 12 nmol.10(6) cells-1.min-1. Hepatocytes from fed rats maintained viability for almost 180 min of anaerobic incubation and then rapidly became damaged. Addition of fructose prevented hypoxic cell damage also in these hepatocytes. Rates of lactate formation were 11-15 nmol.10(6) cells-1.min-1 and were increased two- to threefold by fructose. The rapid initial degradation of glycogen and the release of glucose were delayed with fructose, which also could have contributed to sustained glycolytic rates. Further, under conditions in which lactate production was high, e.g., in the fed state, there was also a significantly better preservation of cellular ATP levels.
authors.affiliation: Institut für Physiologische Chemie I, Universität Düsseldorf, Federal Republic of Germany.
authors.forename: I
authors.initials: I
authors.lastname: Anundi
authors.forename: H
authors.initials: H
authors.lastname: de Groot
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D005215:Fasting; D005502:Food; D005632:Fructose / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000008:administration & dosage / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007773:Lactates; D005632:Fructose; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose; D010100:Oxygen