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| Document type |
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Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
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| Abstract |
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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. |
| Publication date |
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2001 |
| Journal information |
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"Biochimica et biophysica acta" - Vol. 1568, no. 3, p. 245-51 (2001) |
| Peer reviewed |
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yes |
| issn |
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0006-3002 |
| Publication status |
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Publié |
| Affiliation |
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UCL |
| MESH Subject |
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Adenosine Triphosphate - analysis ; Animals ; Aryl Hydrocarbon Hydroxylases ; Biotransformation ; Cold ; Cryopreservation ; Cytochrome P-450 Enzyme System - analysis ; Energy Metabolism ; Glutathione - analysis ; Lipopolysaccharides ; Liver ; Male ; Midazolam - chemistry ; Oxidation-Reduction ; Oxygen ; Rats ; Rats, Wistar ; Steroid Hydroxylases - analysis ; Time Factors
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