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A mechanistic study on the interaction effects between legacy and pollutants of emerging concern

2024-12-15Artigo científico Acesso aberto
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dc.contributor.authorMartins, Carla
dc.contributor.authorCarvalho, Lara M.
dc.contributor.authorCabral, Inês Moutinho
dc.contributor.authorSaúde, Leonor
dc.contributor.authorDreij, Kristian
dc.contributor.authorCosta, Pedro M.
dc.contributor.institutionFaculdade de Ciências e Tecnologia (FCT)
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.pblElsevier
dc.date.accessioned2025-02-05T21:19:35Z
dc.date.available2025-02-05T21:19:35Z
dc.date.issued2024-12-15
dc.descriptionWe are also thankful to C. Gon\u00E7alves and M. D'Ambrosio (UCIBIO) for assistance with the Comet assay protocol. Publisher Copyright: © 2024 The Authors
dc.description.abstractTo study the intricate toxicological mechanisms triggered by exposure to mixed pollutants, we exposed zebrafish embryos to legacy and emerging pollutants through binary mixtures of benzo[a]pyrene (B[a]P) and diclofenac (DFC). The combination of next-generation transcriptomics and toxicopathology disclosed instances where exposure to mixtures did not attain the expected sum of acute effects of individual toxicants, indicating potential antagonism. Despite overall higher mortality in DFC treatments, the same antagonistic trend was noted in genotoxicity and molecular pathways related to RNA turnover, cell proliferation, apoptosis and cell-cycle control. The formation of oedemas in the heart cavity and yolk sac can be an adverse outcome (AO) resulting from exposure to DFC isolated or combined, whose potential key events (KEs) may involve cell cycle arrest and apoptosis via p53 and MAPK pathways. From the findings it can be hypothesised that, rather than genotoxicity, the molecular initiating event (MIE) maybe inflammation triggered by oxidative stress. Nonetheless, the exact role of ROS in the process needs further clarification. Impaired eye function by action of DFC and B[a]P combined may be another AO, in the case caused by ocular degeneration following the suppression of biologic processes and molecular functions involved in eye development and its functionalities, possibly linked to hindered regulation of the expression of hsf4 and cryaa. Altogether, toxicopathology suggests predominance of antagonistic effects, but its integration with mechanism suggests that interactions between DFC and B[a]P in environmentally-relevant concentrations that may lead to hindrance of key functions such as the control of inflammation and cell cycle. These outcomes suggest potentially severe implications for health and survival, in case of prolonged chronic exposure to combined toxicants.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent8201571
dc.identifier.doi10.1016/j.envpol.2024.125189
dc.identifier.issn0269-7491
dc.identifier.otherPURE: 107717841
dc.identifier.otherPURE UUID: 00b35b37-e96e-40fc-b742-6ca9cc681898
dc.identifier.otherScopus: 85208320277
dc.identifier.otherPubMed: 39454814
dc.identifier.otherWOS: 001355934500001
dc.identifier.urihttp://hdl.handle.net/10362/178498
dc.identifier.urlhttps://www.scopus.com/pages/publications/85208320277
dc.language.isoeng
dc.peerreviewedyes
dc.relationFunding Information: info:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F120030%2F2016/PT
dc.relationinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT
dc.relationApplied Molecular Biosciences Unit
dc.relationApplied Molecular Biosciences Unit
dc.relationInstitute for Health and Bioeconomy
dc.subjectBenzo[a]pyrene
dc.subjectMixture
dc.subjectNSAID
dc.subjectPathway analysis
dc.subjectTranscriptomics
dc.subjectZebrafish
dc.subjectToxicology
dc.subjectPollution
dc.subjectHealth, Toxicology and Mutagenesis
dc.titleA mechanistic study on the interaction effects between legacy and pollutants of emerging concernen
dc.title.subtitleA case study with B[a]P and diclofenacen
dc.typejournal article
degois.publication.titleEnvironmental Pollution
degois.publication.volume363
dspace.entity.typePublication
oaire.awardNumberUIDP/04378/2020
oaire.awardNumberUIDB/04378/2020
oaire.awardNumberLA/P/0140/2020
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleInstitute for Health and Bioeconomy
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0140%2F2020/PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
relation.isProjectOfPublication38373452-5c9c-4724-8def-f03314ecce0e
relation.isProjectOfPublicatione07cf232-4705-4b5b-b2c4-af8f25311076
relation.isProjectOfPublication834c369e-6900-4105-aa78-6ba0e52f96ca
relation.isProjectOfPublication.latestForDiscovery38373452-5c9c-4724-8def-f03314ecce0e

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