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Cellular effects of Titanium Dioxide Nanoparticles in the intestine

dc.contributor.authorRolo, Dora
dc.contributor.authorPereira, Joana F.S.
dc.contributor.authorMatos, Paulo
dc.contributor.authorGonçalves, Lídia
dc.contributor.authorBettencourt, Ana Francisca
dc.contributor.authorJordan, Peter
dc.contributor.authorSilva, Maria João
dc.contributor.authorLouro, Henriqueta
dc.date.accessioned2022-01-10T16:26:59Z
dc.date.available2022-01-10T16:26:59Z
dc.date.issued2021-04-20
dc.description.abstractIntroduction: The increased use of titanium dioxide nanoparticles (TiO2-NPs) as a food additive demands a thorough assessment of their potential risk for human health. Via oral exposure they may lead to adverse local or systemic outcomes, and few studies have focused on the cellular internalization mechanisms (endocytosis) of TiO2-NPs. The objective was to analyze the mechanisms by which TiO2-NPs (NM-102, NM-103 and NM-105, JRC repository) translocate by the intestinal epithelium layer, using monolayers of human intestinal cell lines (Caco-2 and HT29-MTX), as well as polarized Caco-2 cells, and co-cultures of both cells. Results: We evaluated cell differentiation by transepithelial resistance measurements and the translocation of TiO2-NPs tagged with alizarin through the intestinal barrier by confocal microscopy and we confirmed the internalization of the TiO2-NPs in both cell line models. Co-localization studies suggested that the smallest TiO2-NPs were internalized into EEA1-positive early-endosomes and accumulate in late endosomes (Rab7), with only a small fraction following the degradative pathway to the lysosome (LAMP1). This suggested that at least part of the TiO2-NPs could be redirected to the secretory pathway. Consistently, we detected fluorescence passing from the apical (AP) to the basolateral (BL) chamber, depending on the characteristics of cell model and TiO2-NPs tested. Conclusions: Small TiO2-NPs were endocytosed by Caco-2 cells, with an increase in particle diameter suggesting intracellular aggregation, whereas larger agglomerates deposited mainly extracellularly. Following endocytosis, TiO2 NPs were trafficked through different intracellular compartments including early and late endosomes/endo-lysosomes, with part being subjected to AP to BL transport.pt_PT
dc.description.abstractSummary: TiO2-NPs may be translocated across the intestinal epithelium layer; This study contributes to a better mechanistic understanding of in vitro TiO2-NPs kinetics as well as their potential fate and effects on humans; It is expected that such an approach will reduce uncertainties in the hazard assessment of ingested TiO2-NPs for human health.pt_PT
dc.description.sponsorshipWork funded by FCT/MCTES through national funds (PIDDAC), PTDC/SAU-PUB/29481/2017 iMed.ULisboa (UID/DTP/04138/2018), and co-funded by ToxOmics(UIDB/00009/2020; UIDP/00009/2020). LG has a Principal Researcher Grant CEECIND/03143/2017.pt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/7843
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationUID/DTP/04138/2018pt_PT
dc.relationCentre for Toxicogenomics and Human Health
dc.subjectIngested Nanomaterialspt_PT
dc.subjectCellular Effectspt_PT
dc.subjectEnvironmental Genotoxicitypt_PT
dc.subjectGenotoxicidade Ambientalpt_PT
dc.subjectVias de Transdução de Sinal e Patologias Associadaspt_PT
dc.titleCellular effects of Titanium Dioxide Nanoparticles in the intestinept_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleCentre for Toxicogenomics and Human Health
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-PUB%2F29481%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00009%2F2020/PT
oaire.citation.conferencePlace(online)pt_PT
oaire.citation.title10th International Conference on Nanotoxicology (NANOTOX), 20-22 april 2021pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameRolo
person.familyNameSilva
person.familyNameLouro
person.givenNameDora
person.givenNameMaria Joao
person.givenNameHenriqueta
person.identifier157627
person.identifier.ciencia-id7E16-CFCA-B797
person.identifier.ciencia-id7710-643D-97A3
person.identifier.ciencia-id721D-2BB1-7DB1
person.identifier.orcid0000-0003-4327-2279
person.identifier.orcid0000-0002-6060-0716
person.identifier.orcid0000-0001-9744-7332
person.identifier.scopus-author-id55944437600
person.identifier.scopus-author-id6507971479
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
rcaap.rightsrestrictedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
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