| Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1. | |
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MedLine Citation:
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PMID: 8194125 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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M P Miguez; I Anundi; L A Sainz-Pardo; K O Lindros |
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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: Chemico-biological interactions Volume: 91 ISSN: 0009-2797 ISO Abbreviation: Chem. Biol. Interact. Publication Date: 1994 Apr |
Date Detail:
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Created Date: 1994-06-24 Completed Date: 1994-06-24 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0227276 Medline TA: Chem Biol Interact Country: IRELAND |
Other Details:
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Languages: eng Pagination: 51-63 Citation Subset: IM |
Affiliation:
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Biomedical Research Center, ALKO Ltd, Helsinki, Finland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Propanol
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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:
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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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