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
HERO ID
4933751
Reference Type
Journal Article
Subtype
Review
Year
2018
Language
English
PMID
| HERO ID | 4933751 |
|---|---|
| Material Type | Review |
| In Press | No |
| Year | 2018 |
| Title | 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 |
| Authors | Hakkola, J; Bernasconi, C; Coecke, S; Richert, L; Andersson, TB; Pelkonen, O |
| Journal | Basic & Clinical Pharmacology & Toxicology |
| Volume | 123 |
| Issue | Suppl 5 Special Issue |
| Page Numbers | 42-50 |
| Abstract | 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. |
| Doi | 10.1111/bcpt.13004 |
| Pmid | 29527807 |
| Wosid | WOS:000445849900006 |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | Helsinki, Finland |
| Conference Name | 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 |
| Conference Date | June 14-16, 2017 |
| Is Public | Yes |
| Language Text | English |
| Is Peer Review | Yes |
| Relationship(s) |
|