Effect of silybin and its glycosides on the expression of cytochromes P450 1A2 and 3A4 in primary cultures of human hepatocytes

✍ Scribed by Pavel Kosina; Patrick Maurel; Jitka Ulrichová; Zdeněk Dvořák

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 203 KB
• Volume: 19
• Category: Article
• ISSN: 1095-6670
• DOI: 10.1002/jbt.20066

✦ Synopsis

Abstract

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