Cargando…

Metabolism of the Marine Phycotoxin PTX-2 and Its Effects on Hepatic Xenobiotic Metabolism: Activation of Nuclear Receptors and Modulation of the Phase I Cytochrome P450

PTX-2 is a marine biotoxin frequently found in shellfish that can lead to food intoxication in humans. Information regarding PTX-2 metabolism is scarce, and little is known of its effect on xenobiotic-metabolizing enzymes (XME) or its molecular pathways. The aim of this study was consequently to exa...

Descripción completa

Detalles Bibliográficos
Autores principales: Alarcan, Jimmy, Dubreil, Estelle, Huguet, Antoine, Hurtaud-Pessel, Dominique, Hessel-Pras, Stefanie, Lampen, Alfonso, Fessard, Valérie, Le Hegarat, Ludovic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535159/
https://www.ncbi.nlm.nih.gov/pubmed/28678150
http://dx.doi.org/10.3390/toxins9070212
_version_ 1783253823097143296
author Alarcan, Jimmy
Dubreil, Estelle
Huguet, Antoine
Hurtaud-Pessel, Dominique
Hessel-Pras, Stefanie
Lampen, Alfonso
Fessard, Valérie
Le Hegarat, Ludovic
author_facet Alarcan, Jimmy
Dubreil, Estelle
Huguet, Antoine
Hurtaud-Pessel, Dominique
Hessel-Pras, Stefanie
Lampen, Alfonso
Fessard, Valérie
Le Hegarat, Ludovic
author_sort Alarcan, Jimmy
collection PubMed
description PTX-2 is a marine biotoxin frequently found in shellfish that can lead to food intoxication in humans. Information regarding PTX-2 metabolism is scarce, and little is known of its effect on xenobiotic-metabolizing enzymes (XME) or its molecular pathways. The aim of this study was consequently to examine PTX-2 Phase I metabolism using rat and human liver S9 fractions, and also to assess the capability of PTX-2: (i) to modulate the gene expression of a panel of Phase I (CYP450) and II (UGT, SULT, NAT, and GST) enzymes, as well as the Phase III or 0 (ABC and SLCO) transporters in the human hepatic HepaRG cell line using qPCR; (ii) to induce specific CYP450 in HepaRG cells measured by immunolabeling detection and the measurement of the cells’ activities; and (iii) to activate nuclear receptors and induce CYP promoter activities in HEK-T and HepG2 transfected cell lines using transactivation and reporter gene assay, respectively. Our results indicate that PTX-2 hydroxylation occurred with both rat and human S9 fractions. Whereas PTX-2 mostly upregulated the gene expression of CYP1A1 and 1A2, no induction of these two CYP activities was observed. Lastly, PTX-2 did not act as an agonist of CAR or PXR. Due to its effects on some key XME, more attention should be paid to possible drug–drug interactions with phycotoxins, especially as shellfish can accumulate several phycotoxins as well as other kinds of contaminants.
format Online
Article
Text
id pubmed-5535159
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-55351592017-08-04 Metabolism of the Marine Phycotoxin PTX-2 and Its Effects on Hepatic Xenobiotic Metabolism: Activation of Nuclear Receptors and Modulation of the Phase I Cytochrome P450 Alarcan, Jimmy Dubreil, Estelle Huguet, Antoine Hurtaud-Pessel, Dominique Hessel-Pras, Stefanie Lampen, Alfonso Fessard, Valérie Le Hegarat, Ludovic Toxins (Basel) Article PTX-2 is a marine biotoxin frequently found in shellfish that can lead to food intoxication in humans. Information regarding PTX-2 metabolism is scarce, and little is known of its effect on xenobiotic-metabolizing enzymes (XME) or its molecular pathways. The aim of this study was consequently to examine PTX-2 Phase I metabolism using rat and human liver S9 fractions, and also to assess the capability of PTX-2: (i) to modulate the gene expression of a panel of Phase I (CYP450) and II (UGT, SULT, NAT, and GST) enzymes, as well as the Phase III or 0 (ABC and SLCO) transporters in the human hepatic HepaRG cell line using qPCR; (ii) to induce specific CYP450 in HepaRG cells measured by immunolabeling detection and the measurement of the cells’ activities; and (iii) to activate nuclear receptors and induce CYP promoter activities in HEK-T and HepG2 transfected cell lines using transactivation and reporter gene assay, respectively. Our results indicate that PTX-2 hydroxylation occurred with both rat and human S9 fractions. Whereas PTX-2 mostly upregulated the gene expression of CYP1A1 and 1A2, no induction of these two CYP activities was observed. Lastly, PTX-2 did not act as an agonist of CAR or PXR. Due to its effects on some key XME, more attention should be paid to possible drug–drug interactions with phycotoxins, especially as shellfish can accumulate several phycotoxins as well as other kinds of contaminants. MDPI 2017-07-05 /pmc/articles/PMC5535159/ /pubmed/28678150 http://dx.doi.org/10.3390/toxins9070212 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alarcan, Jimmy
Dubreil, Estelle
Huguet, Antoine
Hurtaud-Pessel, Dominique
Hessel-Pras, Stefanie
Lampen, Alfonso
Fessard, Valérie
Le Hegarat, Ludovic
Metabolism of the Marine Phycotoxin PTX-2 and Its Effects on Hepatic Xenobiotic Metabolism: Activation of Nuclear Receptors and Modulation of the Phase I Cytochrome P450
title Metabolism of the Marine Phycotoxin PTX-2 and Its Effects on Hepatic Xenobiotic Metabolism: Activation of Nuclear Receptors and Modulation of the Phase I Cytochrome P450
title_full Metabolism of the Marine Phycotoxin PTX-2 and Its Effects on Hepatic Xenobiotic Metabolism: Activation of Nuclear Receptors and Modulation of the Phase I Cytochrome P450
title_fullStr Metabolism of the Marine Phycotoxin PTX-2 and Its Effects on Hepatic Xenobiotic Metabolism: Activation of Nuclear Receptors and Modulation of the Phase I Cytochrome P450
title_full_unstemmed Metabolism of the Marine Phycotoxin PTX-2 and Its Effects on Hepatic Xenobiotic Metabolism: Activation of Nuclear Receptors and Modulation of the Phase I Cytochrome P450
title_short Metabolism of the Marine Phycotoxin PTX-2 and Its Effects on Hepatic Xenobiotic Metabolism: Activation of Nuclear Receptors and Modulation of the Phase I Cytochrome P450
title_sort metabolism of the marine phycotoxin ptx-2 and its effects on hepatic xenobiotic metabolism: activation of nuclear receptors and modulation of the phase i cytochrome p450
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535159/
https://www.ncbi.nlm.nih.gov/pubmed/28678150
http://dx.doi.org/10.3390/toxins9070212
work_keys_str_mv AT alarcanjimmy metabolismofthemarinephycotoxinptx2anditseffectsonhepaticxenobioticmetabolismactivationofnuclearreceptorsandmodulationofthephaseicytochromep450
AT dubreilestelle metabolismofthemarinephycotoxinptx2anditseffectsonhepaticxenobioticmetabolismactivationofnuclearreceptorsandmodulationofthephaseicytochromep450
AT huguetantoine metabolismofthemarinephycotoxinptx2anditseffectsonhepaticxenobioticmetabolismactivationofnuclearreceptorsandmodulationofthephaseicytochromep450
AT hurtaudpesseldominique metabolismofthemarinephycotoxinptx2anditseffectsonhepaticxenobioticmetabolismactivationofnuclearreceptorsandmodulationofthephaseicytochromep450
AT hesselprasstefanie metabolismofthemarinephycotoxinptx2anditseffectsonhepaticxenobioticmetabolismactivationofnuclearreceptorsandmodulationofthephaseicytochromep450
AT lampenalfonso metabolismofthemarinephycotoxinptx2anditseffectsonhepaticxenobioticmetabolismactivationofnuclearreceptorsandmodulationofthephaseicytochromep450
AT fessardvalerie metabolismofthemarinephycotoxinptx2anditseffectsonhepaticxenobioticmetabolismactivationofnuclearreceptorsandmodulationofthephaseicytochromep450
AT lehegaratludovic metabolismofthemarinephycotoxinptx2anditseffectsonhepaticxenobioticmetabolismactivationofnuclearreceptorsandmodulationofthephaseicytochromep450