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Evaluation of genotoxic and mitotoxic effects of TAF-loaded chitosan nanoparticles in HepG2 cells.
Korkmaz Sezer, Selcen; Yuksel, Sengul; Koc, Ahmet; Ulu, Ahmet; Ates, Burhan.
Afiliación
  • Korkmaz Sezer S; Faculty of Medicine, Department of Medical Genetics, Inonu University, Malatya, Turkey.
  • Yuksel S; Faculty of Medicine, Department of Medical Genetics, Inonu University, Malatya, Turkey.
  • Koc A; Faculty of Medicine, Department of Medical Genetics, Inonu University, Malatya, Turkey.
  • Ulu A; Inonu University, Drug Research and Application Center, Malatya, Turkey.
  • Ates B; Faculty of Arts and Science, Department of Chemistry, Malatya, Turkey.
Drug Chem Toxicol ; 47(5): 516-526, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38726977
ABSTRACT
Tenofovir 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 µM TAF-loaded CHS and TAF-only on HepG2 cells by micronucleus (MN), comet assay, determination of mtDNA quantification, mitochondrial membrane potential (ΔΨm), 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 ΔΨm 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Pruebas de Micronúcleos / Especies Reactivas de Oxígeno / Quitosano / Potencial de la Membrana Mitocondrial / Nanopartículas / Tenofovir Límite: Humans Idioma: En Revista: Drug Chem Toxicol Año: 2024 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Pruebas de Micronúcleos / Especies Reactivas de Oxígeno / Quitosano / Potencial de la Membrana Mitocondrial / Nanopartículas / Tenofovir Límite: Humans Idioma: En Revista: Drug Chem Toxicol Año: 2024 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Estados Unidos