Examination of Zolpidem effects on AhR- and PXR-dependent expression of drug-metabolizing cytochromes P450 in primary cultures of human hepatocytes
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19686824
DOI
10.1016/j.toxlet.2009.08.009
PII: S0378-4274(09)01391-5
Knihovny.cz E-resources
- MeSH
- Adult MeSH
- Hepatocytes drug effects enzymology MeSH
- Hypnotics and Sedatives pharmacology MeSH
- Cells, Cultured MeSH
- Pharmaceutical Preparations metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Luciferases genetics MeSH
- RNA, Messenger biosynthesis genetics MeSH
- Plasmids genetics MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Pregnane X Receptor MeSH
- Pyridines pharmacology MeSH
- Receptors, Aryl Hydrocarbon drug effects MeSH
- Aged MeSH
- Receptors, Steroid drug effects MeSH
- Cytochrome P-450 Enzyme System biosynthesis metabolism MeSH
- Transfection MeSH
- Zolpidem MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Hypnotics and Sedatives MeSH
- Pharmaceutical Preparations MeSH
- Luciferases MeSH
- RNA, Messenger MeSH
- Pregnane X Receptor MeSH
- Pyridines MeSH
- Receptors, Aryl Hydrocarbon MeSH
- Receptors, Steroid MeSH
- Cytochrome P-450 Enzyme System MeSH
- Zolpidem MeSH
A hypnotic drug Zolpidem is used in clinical practice for more than 25 years. Surprisingly, the effects of Zolpidem on the expression of drug-metabolizing cytochromes P450 (CYPs) were not examined yet. Recently, the unexpected capacity of several "old drugs", such as valproic acid or azoles, to induce CYPs was reported. Therefore, we tested whether Zolpidem induces the expression of important CYPs in primary cultures of human hepatocytes. Cells were treated for 24h with Zolpidem in therapeutic (0.1mg/L) and toxic (1mg/L) concentrations. The levels of CYP1A1, CYP1A2, CY2C9 and CYP3A4 mRNAs were not altered by Zolpidem, whereas model inducers dioxin and rifampicin significantly induced CYP1A and CYP2/3 gene expression, respectively. Consistently, Zolpidem did not activate aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR), the key regulators of cytochromes P450s, as revealed by transient transfection gene reporter assays using HepG2 cells. We conclude Zolpidem be considered a safe drug with respect to the possible interactions through AhR- and PXR-dependent induction of drug-metabolizing CYPs.
References provided by Crossref.org
Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene
