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

Abstract

Cultured rat precision-cut liver slices (PCLS) were used to study the influence of hypothermic preservation and reoxygenation at 37degreesC on cellular metabolism and drug biotransformation. Cold hypoxic storage caused a depressed metabolism in rat liver slices, but reoxygenation for 8 h at 37degreesC 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 37degreesC 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. (C) 2001 Elsevier Science B.V. All rights reserved.

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Título según WOS: ID WOS:000173570800009 Not found in local WOS DB
Título de la Revista: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volumen: 1568
Número: 3
Editorial: Elsevier
Fecha de publicación: 2001
Página de inicio: 245
Página final: 251
DOI:

10.1016/S0304-4165(01)00225-2

Notas: ISI