1: Biochim Biophys Acta  2001 Dec 19;1568(3):245-51

Reoxygenation after cold hypoxic storage of cultured precision-cut rat liver
slices: effects on cellular metabolism and drug biotransformation.

Rekka E, Evdokimova E, Eeckhaudt S, Calderon PB.

Unite de Pharmacocinetique, Metabolisme, Nutrition et Toxicologie, Departement
de Sciences Pharmaceutiques, Universite Catholique de Louvain, Louvain, Belgium

Cultured rat precision-cut liver slices (PCLS) were used to study the influence
of hypothermic preservation and reoxygenation at 37 degrees C on cellular
metabolism and drug biotransformation. Cold hypoxic storage caused a depressed
metabolism in rat liver slices, but reoxygenation for 8 h at 37 degrees C
partially restored the levels of both ATP and GSH and totally restored the
capacity to synthesize proteins. Metabolism of midazolam (CYP3A-dependent
oxidation) by cold preserved liver slices was decreased by 30% but no further
affected by reoxygenation, showing the same profile as freshly cut slices. Such
a reoxygenation at 37 degrees C is accompanied by a dramatic loss of CYP3A2
protein while CYP3A1 protein was unaffected. These results suggest that CYP3A2
did not play a major role in midazolam oxidation. Such results are not
consistent with a putative reoxygenation injury but rather with cold hypoxic
damage. Since cold preserved liver slices did not respond to bacterial endotoxin
stimulation (lipopolysaccharides), a minor role of non-parenchymal cells is
suggested as mediators for deleterious effects developed during the cold
storage.

PMID: 11786231 [PubMed - in process]