About: Examination of Zolpidem effects on AhR- and PXR-dependent expression of drug-metabolizing cytochromes P450 in primary cultures of human hepatocytes

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About: Examination of Zolpidem effects on AhR- and PXR-dependent expression of drug-metabolizing cytochromes P450 in primary cultures of human hepatocytes Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	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 %22old drugs%22, such as valproic acid orazoles, 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 24 h with Zolpidem in therapeutic (0.1 mg/L) and toxic(l mg/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 d 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 %22old drugs%22, such as valproic acid orazoles, 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 24 h with Zolpidem in therapeutic (0.1 mg/L) and toxic(l mg/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 d (en)
Title	Examination of Zolpidem effects on AhR- and PXR-dependent expression of drug-metabolizing cytochromes P450 in primary cultures of human hepatocytes Examination of Zolpidem effects on AhR- and PXR-dependent expression of drug-metabolizing cytochromes P450 in primary cultures of human hepatocytes (en)
skos:prefLabel	Examination of Zolpidem effects on AhR- and PXR-dependent expression of drug-metabolizing cytochromes P450 in primary cultures of human hepatocytes Examination of Zolpidem effects on AhR- and PXR-dependent expression of drug-metabolizing cytochromes P450 in primary cultures of human hepatocytes (en)
skos:notation	RIV/61989592:15310/09:00010918!RIV10-GA0-15310___
http://linked.open...avai/riv/aktivita	P
http://linked.open...avai/riv/aktivity	P(GA303/07/0128), P(GP303/08/P137), P(GP305/08/P089)
http://linked.open...iv/cisloPeriodika	1
http://linked.open...vai/riv/dodaniDat	2010
http://linked.open...aciTvurceVysledku	Cvek, Boris Vrzal, Radim Dvořák, Zdeněk BACHLEDA, Petr Pivnička, Jakub
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Palackého v Olomouci / Přírodovědecká fakulta
http://linked.open...dnocenehoVysledku	314103
http://linked.open...ai/riv/idVysledku	RIV/61989592:15310/09:00010918
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Human hepatocytes; Cytochrome P450; Zolpidem; Enzyme induction (en)
http://linked.open.../riv/klicoveSlovo	Human hepatocytes Cytochrome P450 Enzyme induction Zolpidem
http://linked.open...odStatuVydavatele	IE - Irsko
http://linked.open...ontrolniKodProRIV	[2E949DEE7AD3]
http://linked.open...i/riv/nazevZdroje	Toxicology Letters
http://linked.open...in/vavai/riv/obor	FR
http://linked.open...ichTvurcuVysledku	5 (xsd:int)
http://linked.open...cetTvurcuVysledku	5 (xsd:int)
http://linked.open...vavai/riv/projekt	Influence of dithiocarbamate complexes with Pt(II) and Au(III) on NF-?B pathway in human tumor lines HepG2 and SK-HEP-1 Study on tissue-specific aspects of transcriptional regulation of selected P-450 enzymes and drug transporters. The role of MAP kinases in cellular signalling of aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)
http://linked.open...UplatneniVysledku	2009
http://linked.open...v/svazekPeriodika	191
http://linked.open...iv/tvurceVysledku	Cvek, Boris Dvořák, Zdeněk Vrzal, Radim Bachleda, Petr Pivnička, Jakub
http://linked.open...ain/vavai/riv/wos	000272276700011
issn	0378-4274
number of pages	5 (xsd:int)
http://localhost/t...ganizacniJednotka	15310

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