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Effect of silybin and its glycosides on the expression of cytochromes P450 1A2 and 3A4 in primary cultures of human hepatocytes
Author(s) -
Kosina Pavel,
Maurel Patrick,
Ulrichová Jitka,
Dvořák Zdeněk
Publication year - 2005
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20066
Subject(s) - cyp3a4 , glycoside , cyp1a2 , chemistry , biochemistry , cytochrome p450 , bioavailability , stereochemistry , pharmacology , enzyme , biology
Four β‐glycosides of flavonoligan silybin, i.e. silybin β‐galactoside, silybin β‐glucoside, silybin β‐maltoside, silybin β‐lactoside were synthesized in order to improve silybin water solubility and bioavailability (Křen et al., J Chem Soc, Perkin Trans 1, 2467–2474, 1997). The presented paper deals with the effect of silybin and its synthetic β‐glycosides on the expression of two major cytochrome P450 isoforms, CYP1A2 and CYP3A4. Primary cultures of human hepatocytes were the model of choice. mRNAs were analyzed using Northern blot and P‐radiolabelled probes. CYP protein content was determined by immunoblotting using specific antibodies. Silybin and its β‐glycosides do not induce expression of CYP1A2 and CYP3A4. Tested compounds did not affect inducible expression of CYP1A2 and CYP3A4 by dioxin and rifampicin, respectively, as evaluated at the level of mRNAs and proteins. Silybin and its β‐glycosides do not interfere with the expression of CYP1A2 and CYP3A4, are not likely to produce drug–drug interactions in terms of the inducibility of two important cytochromes P450. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:149–153, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20066