University of Oulu

Hakkola, J., Bernasconi, C., Coecke, S., Richert, L., Andersson, T. B. and Pelkonen, O. (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 Clin Pharmacol Toxicol, 123: 42-50. doi: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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Author: Hakkola, Jukka1,2; Bernasconi, Camilla3; Coecke, Sandra3;
Organizations: 1Research Unit of Biomedicine, Pharmacology and Toxicology, Faculty of Medicine, University of Oulu
2Medical Research Center Oulu, University of Oulu
3European Commission Joint Research Centre, EURL ECVAM
5Drug Metabolism and Pharmacokinetics, Cardiovascular and Metabolic Diseases, IMED Biotech Unit, AstraZeneca
6Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.1 MB)
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Language: English
Published: John Wiley & Sons, 2018
Publish Date: 2019-01-11


Pregnane 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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Series: Basic & clinical pharmacology & toxicology
ISSN: 1742-7835
ISSN-E: 1742-7843
ISSN-L: 1742-7835
Volume: 123
Issue: S5
Pages: 42 - 50
DOI: 10.1111/bcpt.13004
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
317 Pharmacy
Funding: The original research of the authors (J.H.) has been financially supported by the grants from the Academy of Finland (Grant 286743) and the Novo Nordisk Foundation (Grant NNF15OC0015846) and the Diabetes Research Foundation.
Academy of Finland Grant Number: 286743
Detailed Information: 286743 (Academy of Finland Funding decision)
Copyright information: © 2018 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.