Effect of hypoxia and reoxygenation on metabolic pathways in rat hepatocytes

The mechanisms whereby rat hepatocytes undergo irreversible injury due to a lack of oxygen have not been established.

Liver cells were used for reperfusion injury, and four compartmentalized pathways were evaluated during hypoxia (N2/CO2, 19:1) for 30 min followed by oxygen (O2/CO2, 19:1) for 30 min.

Cell viability decreased during the hypoxic, but not during the reoxygenation, phase. Glycogenolysis, as measured by glucose release, was significantly increased during hypoxia as compared to controls in oxygen (205 +/- 15 vs. 155 +/- 10 nmol glucose/mg protein/h, respectively), and did not return to normal levels by reoxygenation. Gluconeogenesis was importantly decreased during hypoxia (102 +/- 10 vs. 8 +/- 2 nmol glucose/mg protein/h) with partial recovery during reoxygenation. Ureagenesis diminished in hypoxia, but recovered during reoxygenation. Additionally, 3-hydroxybutyrate formation was augmented by hypoxia, with some recovery when oxygen was present.

These results suggest that compartmentalized pathways are protected from hypoxic injury in isolated hepatocytes, and also suggest it as a model to test the idea that enzymes of those pathways are organized into multienzyme complexes in vivo.