Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach

Bioaccumulation of pharmaceuticals in fish exposed to contaminated water can be shaped by their capability to metabolize these xenobiotics, affecting their toxicity and animal welfare. In this study the in vivo metabolization of the antidepressant venlafaxine by the juvenile marine fish meagre (Argy...

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Detalhes bibliográficos
Autores: Santos, Lúcia H. M. L. M., Maulvault, Ana Luísa, Jaén-Gil, Adrián, Marques, Antonio, Barceló, Damià, Rodríguez-Mozaz, Sara
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/216908
Acesso em linha:http://hdl.handle.net/10261/216908
Access Level:acceso abierto
Palavra-chave:Pharmaceuticals
Biotransformations
Fish
Water exposure
LC-HRMS
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spelling Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approachSantos, Lúcia H. M. L. M.Maulvault, Ana LuísaJaén-Gil, AdriánMarques, AntonioBarceló, DamiàRodríguez-Mozaz, SaraPharmaceuticalsBiotransformationsFishWater exposureLC-HRMSBioaccumulation of pharmaceuticals in fish exposed to contaminated water can be shaped by their capability to metabolize these xenobiotics, affecting their toxicity and animal welfare. In this study the in vivo metabolization of the antidepressant venlafaxine by the juvenile marine fish meagre (Argyrosomus regius) was evaluated using a combined target and suspect screening analytical approach. Thirteen venlafaxine metabolites were identified, namely N-desmethylvenlafaxine and N,N-didesmethylvenlafaxine, which were unequivocally identified using analytical standards, and 11 more tentatively identified by suspect screening analysis, including two Phase II metabolites formed by amino acid conjugation. All of them were detected in the liver, while in plasma and brain only 9 and 6 metabolites, respectively, were detected. Based on these findings, for the first time, a tentative metabolization pathway of venlafaxine by A. regius is proposed. Contrarily to what happen in humans, N-demethylation was identified as the main route of metabolization of venlafaxine by fish. Our findings highlight species-specificity in the metabolization of venlafaxine and allow a better understanding of venlafaxine's toxicokinetic in fish. These results emphasize the need to investigate the biotransformation of xenobiotics by non-target organisms to have an integrated overview of their environmental exposure and to improve future evaluations of environmental risk assessment.This work was funded by the 7th EU-FP (ECsafeSEAFOOD project; GA n° 311820) and the European Regional Development Fund (FEDER) and by Spanish Ministry of Economy and Competitiveness (PGE-2010). This work was also funded by the Spanish State Research Agency of the Spanish Ministry of Science, Innovation and Universities and European Fund for Regional Development (project PLAS-MED; FEDER-MCIU-AEI/CTM2017-89701-C3-2-R). Authors thank Generalitat de Catalunya through Consolidated Research Group (ICRA-ENV 2017 SGR 1124 & 2017 SGR 1404). ICRA researchers thank funding from CERCA program. Lúcia H.M.L.M. Santos thanks the Juan de la Cierva program (IJCI-2017-32747) and Sara Rodríguez-Mozaz thanks the Ramon y Cajal program (RYC-2014-16707) from the Spanish State Research Agency of the Spanish Ministry of Science, Innovation and Universities (AEI-MCIU). A. Jaén-Gil thanks the predoctoral grant from the Agency for Management of University and Research Grants (AGAUR) (2019FI_B2_00202) co-financed by the European Social Fund. A. Marques (IF program) and A.L. Maulvault (Project FishBudget PTDC/BIA-BMA/28630/2017) thank the Portuguese Foundation for Science and Technology.Peer reviewedElsevierEuropean CommissionBarceló, Damià [0000-0002-8873-0491]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/216908reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/FP7/311820https://doi.org/10.1016/j.scitotenv.2020.140226Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2169082026-05-22T06:33:51Z
dc.title.none.fl_str_mv Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach
title Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach
spellingShingle Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach
Santos, Lúcia H. M. L. M.
Pharmaceuticals
Biotransformations
Fish
Water exposure
LC-HRMS
title_short Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach
title_full Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach
title_fullStr Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach
title_full_unstemmed Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach
title_sort Insights on the metabolization of the antidepressant venlafaxine by meagre (Argyrosomus regius) using a combined target and suspect screening approach
dc.creator.none.fl_str_mv Santos, Lúcia H. M. L. M.
Maulvault, Ana Luísa
Jaén-Gil, Adrián
Marques, Antonio
Barceló, Damià
Rodríguez-Mozaz, Sara
author Santos, Lúcia H. M. L. M.
author_facet Santos, Lúcia H. M. L. M.
Maulvault, Ana Luísa
Jaén-Gil, Adrián
Marques, Antonio
Barceló, Damià
Rodríguez-Mozaz, Sara
author_role author
author2 Maulvault, Ana Luísa
Jaén-Gil, Adrián
Marques, Antonio
Barceló, Damià
Rodríguez-Mozaz, Sara
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Barceló, Damià [0000-0002-8873-0491]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Pharmaceuticals
Biotransformations
Fish
Water exposure
LC-HRMS
topic Pharmaceuticals
Biotransformations
Fish
Water exposure
LC-HRMS
description Bioaccumulation of pharmaceuticals in fish exposed to contaminated water can be shaped by their capability to metabolize these xenobiotics, affecting their toxicity and animal welfare. In this study the in vivo metabolization of the antidepressant venlafaxine by the juvenile marine fish meagre (Argyrosomus regius) was evaluated using a combined target and suspect screening analytical approach. Thirteen venlafaxine metabolites were identified, namely N-desmethylvenlafaxine and N,N-didesmethylvenlafaxine, which were unequivocally identified using analytical standards, and 11 more tentatively identified by suspect screening analysis, including two Phase II metabolites formed by amino acid conjugation. All of them were detected in the liver, while in plasma and brain only 9 and 6 metabolites, respectively, were detected. Based on these findings, for the first time, a tentative metabolization pathway of venlafaxine by A. regius is proposed. Contrarily to what happen in humans, N-demethylation was identified as the main route of metabolization of venlafaxine by fish. Our findings highlight species-specificity in the metabolization of venlafaxine and allow a better understanding of venlafaxine's toxicokinetic in fish. These results emphasize the need to investigate the biotransformation of xenobiotics by non-target organisms to have an integrated overview of their environmental exposure and to improve future evaluations of environmental risk assessment.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/216908
url http://hdl.handle.net/10261/216908
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/FP7/311820
https://doi.org/10.1016/j.scitotenv.2020.140226
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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