| Morphology and cytochrome P450 isoforms expression in precision-cut rat liver slices. | |
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MedLine Citation:
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PMID: 11295255 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Precision-cut liver slices are a widely accepted in vitro system for the examination of drug metabolism, enzyme induction, or hepatotoxic effects of xenobiotics. The maintenance of the distinct lobular expression and induction pattern of phase I biotransformation enzymes, however, has not been examined systematically so far. Thus, in the present study, both longitudinal and transversal sections of male rat liver slices were investigated morphologically, as well as immunohistochemically for the expression of different cytochrome P450 (CYP) isoforms after prolonged incubation or after exposure to typical inducers. Histopathological examinations revealed an increasing vacuolization of the periportal hepatocytes mainly in the middle of the slices from 6 h of incubation on, paralleled by a loss of glycogen in the respective cells. After 24 h, mainly in the center of the slices, necroses of cells occurred. After 48 h of incubation, typically a central band of coagulative necrosis flanked by superficial layers of viable cells was observed. Freshly prepared slices displayed a CYP subtypes expression as normal liver specimen, a very low centrilobular CYP 1A1 immunostaining, but a strong CYP 2B1 and 3A2 expression predominantly in the central and intermediate lobular zones. From 2 h on, the immunostaining for CYP 2B1 and 3A2 was to some extent reduced. After 24 h of incubation with beta-naphthoflavone, the CYP 1A1 and 2B1 expression was induced mainly in the viable cells around central veins, around some portal fields with bigger vessels and in the cell layers close to the slice surface. At the same sites, phenobarbital led to an increased CYP 2B1 and 3A2 expression and dexamethasone to an elevated CYP 3A2 immunostaining. These results show, that an in vitro induction of phase I enzymes in precision-cut liver slices can be demonstrated also immunohistochemically. |
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Authors:
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A Lupp; M Danz; D Müller |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Toxicology Volume: 161 ISSN: 0300-483X ISO Abbreviation: Toxicology Publication Date: 2001 Mar |
Date Detail:
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Created Date: 2001-04-11 Completed Date: 2001-05-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: Ireland |
Other Details:
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Languages: eng Pagination: 53-66 Citation Subset: IM |
Affiliation:
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Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Nonnenplan 4, D-07743, Jena, Germany. alup@mti-n.uni-jena.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents / pharmacology* Anticonvulsants / pharmacology Cells, Cultured Cytochrome P-450 Enzyme System / biosynthesis, metabolism* Dexamethasone / pharmacology* Enzyme Induction / drug effects Enzyme Inhibitors / pharmacology* Glycogen / metabolism* Isoenzymes Liver / drug effects*, enzymology*, metabolism Male Phenobarbital / pharmacology Rats beta-Naphthoflavone / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 0/Anticonvulsants; 0/Enzyme Inhibitors; 0/Isoenzymes; 50-02-2/Dexamethasone; 50-06-6/Phenobarbital; 6051-87-2/beta-Naphthoflavone; 9005-79-2/Glycogen; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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