Document Detail


Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1.
MedLine Citation:
PMID:  8194125     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The involvement of the alcohol-inducible cytochrome P450 2E1 in the hepatoprotective mechanism of the plant flavonoid extract silymarin, and its main active component silybin, was investigated in isolated hepatocytes. Allyl alcohol toxicity, associated lipid peroxidation and GSH depletion was efficiently counteracted by silymarin (0.01-0.5 mM), and at higher concentrations by silybin. Cell damage by t-butyl hydroperoxide was also prevented by silymarin and silybin, but less efficiently. However, the covalent binding of the acetaminophen intermediate, formed via P450 2E1, was unaffected by addition of the flavonoids. Silybin did not influence microsomal 2E1-catalyzed demethylation of N-nitrosodimethylamine. Neither did demethylation of N-nitrosodimethylamine or aminopyrine by isolated microsomes affect the in vivo administration of silybin. Addition of silymarin or silybin to primary cultures of isolated hepatocytes did not prevent cell damage induced by exposure to the P450 2E1 substrate CCl4. In contrast, the mere presence of low concentrations (25-50 microM) of these compounds was found to inhibit cell attachment to the matrix and eventually resulted in cell damage. We conclude that contrary to earlier reports we found no evidence for an interaction of silymarin or silybin with cytochrome P450 2E1. This suggests that the antioxidant and free radical scavenging properties may account for most of the therapeutic effect of these compounds. The untoward effect of silymarin on cultured cells may have consequences when considering long-term prescription of this therapeutic agent.
Authors:
M P Miguez; I Anundi; L A Sainz-Pardo; K O Lindros
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  91     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-06-24     Completed Date:  1994-06-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  51-63     Citation Subset:  IM    
Affiliation:
Biomedical Research Center, ALKO Ltd, Helsinki, Finland.
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MeSH Terms
Descriptor/Qualifier:
1-Propanol / pharmacology
Animals
Cytochrome P-450 CYP2E1
Cytochrome P-450 Enzyme System / drug effects*,  metabolism
Enzyme Induction
Glutathione / drug effects
Lipid Peroxidation / drug effects
Liver / drug effects*,  enzymology
Male
Oxidoreductases, N-Demethylating / drug effects*,  metabolism
Peroxides / pharmacology
Propanols
Rats
Rats, Wistar
Silymarin / pharmacology*
tert-Butylhydroperoxide
Chemical
Reg. No./Substance:
0/Peroxides; 0/Propanols; 0/Silymarin; 107-18-6/allyl alcohol; 70-18-8/Glutathione; 71-23-8/1-Propanol; 75-91-2/tert-Butylhydroperoxide; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Cytochrome P-450 CYP2E1; EC 1.5.-/Oxidoreductases, N-Demethylating

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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