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Assessing the impact of TiO2 nanomaterials on intestinal cells: New evidence for epithelial translocation and potential pro-inflammatory effects

2025-01-25Journal article Open access
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dc.contributor.authorRolo, Dora
dc.contributor.authorPereira, Joana F.S.
dc.contributor.authorGonçalves, Lídia
dc.contributor.authorBettencourt, Ana
dc.contributor.authorJordan, Peter
dc.contributor.authorSilva, Maria João
dc.contributor.authorMatos, Paulo
dc.contributor.authorLouro, Henriqueta
dc.date.accessioned2025-11-04T15:28:14Z
dc.date.available2025-11-04T15:28:14Z
dc.date.issued2025-01-25
dc.description
dc.description.abstractUnderstanding the potential impact of nanomaterials (NMs) on human health requires further investigation into the organ-specific nano-bio interplay at the cellular and molecular levels. We showed increased chromosomal damage in intestinal cells exposed to some of in vitro digested Titanium dioxide (TiO2) NMs. The present study aimed to explore possible mechanisms linked to the uptake, epithelial barrier integrity, cellular trafficking, as well as activation of pro-inflammatory pathways, after exposure to three TiO2-NMs (NM-102, NM-103, and NM-105). Using confocal microscopy, we show that all NMs, digested or not, were able to enter different types of intestinal cells. At the physiologically relevant concentration of 14 μg/mL, the digested TiO2-NMs did not compromise the transepithelial resistance, nor the levels of epithelial markers E-cadherin and Zonula occludens protein 1 (ZO-1), of polarized enterocyte monolayers. Nonetheless, all NMs were internalized by intestinal cells and, while NM-102 was retained in lysosomes, NM-103 and NM-105 were able to transverse the epithelial barrier through transcytosis. Moreover, 24 h exposure of 14 and 1.4 μg/mL digested NM-105, promoted interleukin IL-1β expression in activated M1 macrophages, indicating a potential pro-inflammatory action in the gut. Taken together, our findings shed light on the cell-specific nano-bio interplay of TiO2-NMs in the context of the intestinal tract and highlight transcytosis as a potential gateway for their systemic distribution. The potential proinflammatory action of digested NM-105 emphasizes the importance of pursuing research into the potential impact of NMs on human health and contribute to the weight of evidence to limit their use in food.eng
dc.description.sponsorshipThis work was funded by national funds through the FCT - Foundation for Science and Technology, I.P., under the project PTDC/SAU- PUB/29481/2017. Research was co-funded by ToxOmics (UIDB/00009/ 2020 and UIDP/00009/2020), BioISI (UID/MULTI/04046/2019), iMed. ULisboa (UIDB/04138/2020 and UIDP/04138/2020), and principal investigator contract CEECIND/03143/2017 (L.G.).
dc.identifier.citationToxicology. 2025 Feb:511:154066. doi: 10.1016/j.tox.2025.154066. Epub 2025 Jan 25
dc.identifier.doi10.1016/j.tox.2025.154066
dc.identifier.eissn1879-3185
dc.identifier.issn0300-483X
dc.identifier.pmid39870156
dc.identifier.urihttp://hdl.handle.net/10400.18/10572
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationCellular and Molecular Mechanisms of Toxicity of Ingested Nanomaterials
dc.relationCentre for Toxicogenomics and Human Health
dc.relationCentre for Toxicogenomics and Human Health
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S0300483X25000228?via%3Dihub54066
dc.relation.ispartofToxicology
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectTitanium Dioxide Nanomaterials
dc.subjectUptake
dc.subjectIntestinal Tract
dc.subjectEnvironmental Genotoxicity
dc.subjectDigestion
dc.subjectEpithelial Barrier
dc.subjectGIT
dc.subjectIngested Nanomaterial
dc.subjectGenotoxicidade Ambiental
dc.titleAssessing the impact of TiO2 nanomaterials on intestinal cells: New evidence for epithelial translocation and potential pro-inflammatory effectseng
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCellular and Molecular Mechanisms of Toxicity of Ingested Nanomaterials
oaire.awardTitleCentre for Toxicogenomics and Human Health
oaire.awardTitleCentre for Toxicogenomics and Human Health
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017/PTDC%2FSAU-PUB%2F29481%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00009%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00009%2F2020/PT
oaire.citation.startPage154066
oaire.citation.titleJournal of Toxicology
oaire.citation.volume511
oaire.fundingStreamConcurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameLouro
person.givenNameHenriqueta
person.identifier157627
person.identifier.ciencia-id721D-2BB1-7DB1
person.identifier.orcid0000-0001-9744-7332
person.identifier.scopus-author-id6507971479
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
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