Document Detail

Morphology and cytochrome P450 isoforms expression in precision-cut rat liver slices.
MedLine Citation:
PMID:  11295255     Owner:  NLM     Status:  MEDLINE    
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.
A Lupp; M Danz; D Müller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology     Volume:  161     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-04-11     Completed Date:  2001-05-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  53-66     Citation Subset:  IM    
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Nonnenplan 4, D-07743, Jena, Germany.
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MeSH Terms
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*
Liver / drug effects*,  enzymology*,  metabolism
Phenobarbital / pharmacology
beta-Naphthoflavone / pharmacology*
Reg. No./Substance:
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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