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Statements

Subject Item
n2:RIV%2F61989592%3A15310%2F14%3A33150564%21RIV15-GA0-15310___
rdf:type
skos:Concept n14:Vysledek
rdfs:seeAlso
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0105580
dcterms:description
Benzimidazole drugs lansoprazole and omeprazole are used for treatment of various gastrointestinal pathologies. Both compounds cause drug-drug interactions because they activate aryl hydrocarbon receptor and induce CYP1A genes. In the current paper, we examined the effects of lansoprazole and omeprazole enantiomers on the expression of key drug-metabolizing enzyme CYP3A4 in human hepatocytes and human cancer cell lines. Lansoprazole enantiomers, but not omeprazole, were equipotent inducers of CYP3A4 mRNA in HepG2 cells. All forms (S-, R-, rac-) of lansoprazole and omeprazole induced CYP3A4 mRNA and protein in human hepatocytes. The quantitative profiles of CYP3A4 induction by individual forms of lansoprazole and omeprazole exerted enantiospecific patterns. Lansoprazole dose-dependently activated pregnane X receptor PXR in gene reporter assays, and slightly modulated rifampicin-inducible PXR activity, with similar potency for each enantiomer. Omeprazole dose-dependently activated PXR and inhibited rifampicin-inducible PXR activity. The effects of S- omeprazole were much stronger as compared to those of R- omeprazole. All forms of lansoprazole, but not omeprazole, slightly activated glucocorticoid receptor and augmented dexamethasone-induced GR transcriptional activity. Omeprazole and lansoprazole influenced basal and ligand inducible expression of tyrosine aminotransferase, a GR-target gene, in HepG2 cells and human hepatocytes. Overall, we demonstrate here that omeprazole and lansoprazole enantiomers induce CYP3A4 in HepG2 cells and human hepatocytes. The induction comprises differential interactions of omeprazole and lansoprazole with transcriptional regulators PXR and GR, and some of the effects were enantiospecific. The data presented here might be of toxicological and clinical importance, since the effects occurred in therapeutically relevant concentrations. Benzimidazole drugs lansoprazole and omeprazole are used for treatment of various gastrointestinal pathologies. Both compounds cause drug-drug interactions because they activate aryl hydrocarbon receptor and induce CYP1A genes. In the current paper, we examined the effects of lansoprazole and omeprazole enantiomers on the expression of key drug-metabolizing enzyme CYP3A4 in human hepatocytes and human cancer cell lines. Lansoprazole enantiomers, but not omeprazole, were equipotent inducers of CYP3A4 mRNA in HepG2 cells. All forms (S-, R-, rac-) of lansoprazole and omeprazole induced CYP3A4 mRNA and protein in human hepatocytes. The quantitative profiles of CYP3A4 induction by individual forms of lansoprazole and omeprazole exerted enantiospecific patterns. Lansoprazole dose-dependently activated pregnane X receptor PXR in gene reporter assays, and slightly modulated rifampicin-inducible PXR activity, with similar potency for each enantiomer. Omeprazole dose-dependently activated PXR and inhibited rifampicin-inducible PXR activity. The effects of S- omeprazole were much stronger as compared to those of R- omeprazole. All forms of lansoprazole, but not omeprazole, slightly activated glucocorticoid receptor and augmented dexamethasone-induced GR transcriptional activity. Omeprazole and lansoprazole influenced basal and ligand inducible expression of tyrosine aminotransferase, a GR-target gene, in HepG2 cells and human hepatocytes. Overall, we demonstrate here that omeprazole and lansoprazole enantiomers induce CYP3A4 in HepG2 cells and human hepatocytes. The induction comprises differential interactions of omeprazole and lansoprazole with transcriptional regulators PXR and GR, and some of the effects were enantiospecific. The data presented here might be of toxicological and clinical importance, since the effects occurred in therapeutically relevant concentrations.
dcterms:title
Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis
skos:prefLabel
Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis
skos:notation
RIV/61989592:15310/14:33150564!RIV15-GA0-15310___
n4:aktivita
n15:P
n4:aktivity
P(GA13-01809S)
n4:cisloPeriodika
8
n4:dodaniDat
n7:2015
n4:domaciTvurceVysledku
n12:8069239 n12:5266815
n4:druhVysledku
n17:J
n4:duvernostUdaju
n10:S
n4:entitaPredkladatele
n20:predkladatel
n4:idSjednocenehoVysledku
34197
n4:idVysledku
RIV/61989592:15310/14:33150564
n4:jazykVysledku
n16:eng
n4:klicovaSlova
isomer; enzymes; article; esomeprazole; pharmacokinetics; expression; proton pump inhibitor
n4:klicoveSlovo
n5:enzymes n5:proton%20pump%20inhibitor n5:isomer n5:expression n5:article n5:esomeprazole n5:pharmacokinetics
n4:kodStatuVydavatele
US - Spojené státy americké
n4:kontrolniKodProRIV
[355DF098594B]
n4:nazevZdroje
PLoS One
n4:obor
n13:FR
n4:pocetDomacichTvurcuVysledku
2
n4:pocetTvurcuVysledku
2
n4:projekt
n19:GA13-01809S
n4:rokUplatneniVysledku
n7:2014
n4:svazekPeriodika
9
n4:tvurceVysledku
Dvořák, Zdeněk Novotná, Aneta
n4:wos
000342687200105
s:issn
1932-6203
s:numberOfPages
9
n8:doi
10.1371/journal.pone.0105580
n18:organizacniJednotka
15310