US EPA

4933751 

Journal Article 

Review 

Cytochrome P450 induction and xeno-sensing receptors pregnane X receptor, constitutive androstane receptor, aryl hydrocarbon receptor and peroxisome proliferator-activated receptor α at the crossroads of toxicokinetics and toxicodynamics 

Hakkola, J; Bernasconi, C; Coecke, S; Richert, L; Andersson, TB; Pelkonen, O 

2018 

Yes 

Basic & Clinical Pharmacology & Toxicology
ISSN: 1742-7835
EISSN: 1742-7843 

123 

Suppl 5 Special Issue 

42-50 

English 

29527807 

10.1111/bcpt.13004 

WOS:000445849900006 

is supplemented by 4933792 : Appendix

Pregnane X receptor (PXR), constitutive androstane receptor (CAR), aryl hydrocarbon receptor (AHR) and peroxisome proliferator-activated receptor (PPAR) are ligand-activated transcription factors that regulate expression of many xenobiotic-metabolizing enzymes including several cytochrome P450 (CYP) enzymes. Many xenobiotics induce CYP enzymes through these intracellular receptors and consequently affect toxicokinetics and possible metabolic activation of the receptor ligands and other xenobiotics utilizing similar metabolic pathways. However, it is now apparent that the xenobiotic receptors regulate also many endogenous functions and signalling pathways, and xenobiotic exposure thus may dysregulate an array of fundamental cell functions. This MiniReview surveys and discusses the multifaceted roles of xenobiotic receptors, for which CYP induction may serve as the first alert and possibly a biomarker for exposure to xenobiotics. With the current emergence of the adverse outcome pathway (AOP) concept, these receptors are being and will be assigned as molecular initiating events or key events in numerous discrete toxicity pathways. 

Joint European-Consensus-Platform-for-Alternatives (ECOPA) and Scandinavian-Society-for-Cell-Toxicology (SSCT) Workshop on Up-to-Date in Vitro Approaches in Regulatory Risk Assessment and Disease Modeling 

Helsinki, Finland 

June 14-16, 2017