title: Metabonomic studies on human hepatocyte in primary culture.
abstract: Mechanisms involved in induction processes have been investigated using fresh human hepatocytes in culture as a cellular model and using mass spectrometry-based metabonomics as a global investigation tool. Sample preparation to data analysis have been detailed in an approach enabling to separate drug-induced (endogenous metabolites) and drug-related (drug metabolites) biomarkers for reference inducers. Rifampicin, a nuclear pregnane X receptor (PXR) ligand; CITCO, a nuclear constitutive androstane receptor (CAR) ligand; and phenobarbital, which activates both CAR and PXR, have been used. Specific intra-cellular metabolites have been isolated for rifampicin and CITCO as potential endogenous biomarkers of their respective induction mechanism. A mixture of these two types of biomarkers modified in the same way after treatment with either rifampicin or CITCO on the one hand and with phenobarbital on the other hand has been found.
authors.affiliation: Technologie Servier, Orléans, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Croixmarie
authors.forename: Thierry
authors.initials: T
authors.lastname: Umbdenstock
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: Amélie
authors.initials: A
authors.lastname: Moreau
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Pascussi
authors.forename: Yannick
authors.initials: Y
authors.lastname: Parmentier
authors.forename: Claire
authors.initials: C
authors.lastname: Boursier-Neyret
authors.forename: Bernard
authors.initials: B
authors.lastname: Walther
mesh_terms: D002478:Cells, Cultured; D000090702:Constitutive Androstane Receptor; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods*; D008954:Models, Biological; D010091:Oximes / Q000378:metabolism / Q000494:pharmacology*; D010634:Phenobarbital / Q000378:metabolism / Q000494:pharmacology*; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D012293:Rifampin / Q000378:metabolism / Q000494:pharmacology*; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000090702:Constitutive Androstane Receptor; D010091:Oximes; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013844:Thiazoles; C475093:6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime; D012293:Rifampin; D010634:Phenobarbital