Evaluation of genotoxic and mitotoxic effects of TAF-loaded chitosan nanoparticles in HepG2 cells

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dc.authoridKorkmaz Sezer, Selcen/0000-0001-9479-3176
dc.authoridKoc, Ahmet/0000-0003-3484-2137
dc.authoridYuksel, Sengul/0000-0002-7190-431X
dc.authoridAtes, Burhan/0000-0001-6080-229X
dc.authorwosidKorkmaz Sezer, Selcen/ABU-1678-2022
dc.contributor.authorSezer, Selcen Korkmaz
dc.contributor.authorYuksel, Sengul
dc.contributor.authorKoc, Ahmet
dc.contributor.authorUlu, Ahmet
dc.contributor.authorAtes, Burhan
dc.date.accessioned2024-08-04T20:55:59Z
dc.date.available2024-08-04T20:55:59Z
dc.date.issued2024
dc.departmentİnönü Üniversitesien_US
dc.description.abstractTenofovir alafenamide (TAF) is a new drug from the nucleotide reverse transcriptase inhibitor group approved for the treatment of chronic Hepatitis B in 2016. With this study, we aimed to test whether possible cellular toxicity can be reduced by controlled drug release as a result of loading with chitosan nanoparticles (CHS). We investigated the genotoxic and mitotoxic effects of 45 mu M TAF-loaded CHS and TAF-only on HepG2 cells by micronucleus (MN), comet assay, determination of mtDNA quantification, mitochondrial membrane potential (Delta Psi m), and ROS levels. Additionally, we compared the samples by RNAseq analyses to reveal the transcriptional responses to each regimen. In terms of genotoxic tests, although MN and comet were found higher in all experimental treatment conditions, the encapsulation of CHS reduced the genotoxicity of TAF. MtDNA level was found to be lower in the TAF treatment, whereas it was higher in CHS and CHS-TAF treatments. The TAF-loaded CHS and TAF treatments had an impaired Delta Psi m value. Cellular ROS levels were higher in all treatment conditions. According to the analyses of gene expression patterns; CHS-only changed the expression of relatively few genes (187 genes), while TAF changed the expression of the 1974 genes and TAF-loaded CHS changed the expression of 734 genes. Considering the gene expression numbers, CHS encapsulation of TAF significantly reduced the number of genes that were differentially expressed by TAF-only. Overall, we observed that TAF has genotoxic and mitotoxic effects on HepG2 cells, and upon encapsulation with CHS, its genotoxic and mitotoxic effects were decreased.en_US
dc.description.sponsorshipInonu University Research Fund in Turkey [TCD/2018-1356]en_US
dc.description.sponsorshipThis study was funded by the Inonu University Research Fund in Turkey (TCD/2018-1356).en_US
dc.identifier.doi10.1080/01480545.2024.2349663
dc.identifier.issn0148-0545
dc.identifier.issn1525-6014
dc.identifier.pmid38726977en_US
dc.identifier.scopus2-s2.0-85192715288en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1080/01480545.2024.2349663
dc.identifier.urihttps://hdl.handle.net/11616/101986
dc.identifier.wosWOS:001217825700001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Ltden_US
dc.relation.ispartofDrug and Chemical Toxicologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectWorden_US
dc.subjectcytotoxicityen_US
dc.subjectcontrolled drug releaseen_US
dc.subjectgenotoxicityen_US
dc.subjectmitochondrial toxicityen_US
dc.subjectpharmaceutical toxicologyen_US
dc.subjecttenofovir alafenamideen_US
dc.titleEvaluation of genotoxic and mitotoxic effects of TAF-loaded chitosan nanoparticles in HepG2 cellsen_US
dc.typeArticleen_US

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