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

Jukka Hakkola; Camilla Bernasconi; Sandra Coecke; Lysiane Richert; Tommy B. Andersson; Olavi Pelkonen

doi:10.1111/bcpt.13004

journal article Open Access Apr 29, 2018

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

Jukka Hakkola

Camilla Bernasconi Sandra Coecke Lysiane Richert Tommy B. Andersson Olavi Pelkonen

Basic & Clinical Pharmacology & Toxicology Vol. 123 No. S5 pp. 42-50 · Wiley

View at Publisher Save 10.1111/bcpt.13004

Abstract

AbstractPregnane X receptor (PXR), constitutive androstane receptor (CAR), aryl hydrocarbon receptor (AHR) and peroxisome proliferator‐activated receptor α (PPARα) 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.

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Details

Published: Apr 29, 2018
Vol/Issue: 123(S5)
Pages: 42-50
License: View

Authors

J

Jukka Hakkola

Research Unit of Biomedicine, Pharmacology and Toxicology Faculty of Medicine University of Oulu Oulu Finland; Medical Research Center Oulu University of Oulu Oulu Finland

C

Camilla Bernasconi

European Commission Joint Research Centre EURL ECVAM Ispra Italy

S

Sandra Coecke

European Commission Joint Research Centre EURL ECVAM Ispra Italy

L

Lysiane Richert

KaLy‐Cell Plobsheim France

T

Tommy B. Andersson

Drug Metabolism and Pharmacokinetics Cardiovascular and Metabolic Diseases IMED Biotech Unit AstraZeneca Gothenburg Sweden; Department of Physiology and Pharmacology Section of Pharmacogenetics Karolinska Institutet Stockholm Sweden

O

Olavi Pelkonen

Research Unit of Biomedicine, Pharmacology and Toxicology Faculty of Medicine University of Oulu Oulu Finland; Medical Research Center Oulu University of Oulu Oulu Finland

Funding

Academy of Finland Award: 286743

Cite This Article

Jukka Hakkola, Camilla Bernasconi, Sandra Coecke, et al. (2018). 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. Basic & Clinical Pharmacology & Toxicology, 123(S5), 42-50. https://doi.org/10.1111/bcpt.13004

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

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