Publication Name	World Journal of Gastroenterology
Manuscript ID	35758
Country	Italy

Category	Pharmacology & Pharmacy
Manuscript Type	Basic Study
Article Title	Pregnane X receptor and constitutive androstane receptor modulate differently CYP3A-mediated metabolism in early- and late-stage cholestasis
Manuscript Source	Unsolicited Manuscript
All Author List	Daniela Gabbia, Arianna Dalla Pozza, Laura Albertoni, Roberta Lazzari, Giorgia Zigiotto, Maria Carrara, Vincenzo Baldo, Tatjana Baldovin, Annarosa Floreani and Sara De Martin
Funding Agency and Grant Number	Funding Agency Grant Number Grant from the University of Padova CPDA138721/13
Corresponding Author	Sara De Martin, PharmD, PhD, Assistant Professor, Department of Pharmaceutical and Pharmacological Sciences, University of Padova, L.go Meneghetti, 2, Padova 35131, Italy. sara.demartin@unipd.it
Key Words	Cholestasis; CYP3A; Drug metabolism; Pregnane X receptor; Constitutive androstane receptor
Core Tip	We demonstrated that early- and late-stage cholestasis affects CYP3A-mediated metabolism differently, probably as consequence of the different activation of Pregnane X Receptor (PXR) and Constitutive Androstane Receptor (CAR). As a consequence, cholestatic patients may have an altered drug metabolism: in the early stage due to the induction of CYP3A enzymes; and in the late stage due to the high deposition of fibrotic liver and consequent hepatocyte loss. Secondly, since PXR activation is known to induce alternative hepatic export routes and detoxification enzymes, the induction of these cellular pathways with PXR and/or CAR agonists could be exploited as a therapeutic strategy for the management of cholestatic diseases.
Citation	Gabbia D, Dalla Pozza A, Albertoni L, Lazzari R, Zigiotto G, Carrara M, Baldo V, Baldovin T, Floreani A, De Martin S. pregnane X receptor and constitutive androstane receptor modulate differently CYP3A-mediated metabolism in early- and late-stage cholestasis. World J Gastroenterol 2017; 23(42): 7519-7530

Received	2017-08-05 05:07
Peer-Review Started	2017-08-07 10:04
To Make the First Decision	2017-08-30 02:42
Return for Revision	2017-08-31 07:49
Revised	2017-09-18 09:18
Second Decision	2017-10-11 06:46
Accepted by Journal Editor-in-Chief
Accepted by Company Editor-in-Chief	2017-10-17 20:10
Articles in Press	2017-10-17 20:10
Publication Fee Transferred	2017-10-30 15:06
Edit the Manuscript by Language Editor
Typeset the Manuscript	2017-11-06 04:36

ISSN	1007-9327 (print) and 2219-2840 (online)
Open Access	This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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