Genotoxicity assessment of 1,4-anhydro-4-seleno-D-talitol (SeTal) in human liver HepG2 and HepaRG cells.

Autor: di Vito R; Department of Pharmaceutical Sciences (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: raffaella.divito@outlook.it., Acito M; Department of Pharmaceutical Sciences (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: mattia.acito@unipg.it., Fatigoni C; Department of Pharmaceutical Sciences (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: cristina.fatigoni@unipg.it., Schiesser CH; Seleno Therapeutics Pty. Ltd., Brighton East, Victoria 3187, Australia. Electronic address: carl@selenotherapeutics.com., Davies MJ; Seleno Therapeutics Pty. Ltd., Brighton East, Victoria 3187, Australia; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark. Electronic address: davies@sund.ku.dk., Mangiavacchi F; Department of Pharmaceutical Sciences (Group of Catalysis Synthesis and Organic Green Chemistry), University of Perugia, Via del Liceo, 06123 Perugia, Italy. Electronic address: francesca.mangiavacchi@unipg.it., Villarini M; Department of Pharmaceutical Sciences (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: milena.villarini@unipg.it., Santi C; Department of Pharmaceutical Sciences (Group of Catalysis Synthesis and Organic Green Chemistry), University of Perugia, Via del Liceo, 06123 Perugia, Italy. Electronic address: claudio.santi@unipg.it., Moretti M; Department of Pharmaceutical Sciences (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: massimo.moretti@unipg.it.
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2023 Nov; Vol. 499, pp. 153663. Date of Electronic Publication: 2023 Nov 02.
DOI: 10.1016/j.tox.2023.153663
Abstrakt: 1,4-Anhydro-4-seleno-D-talitol (SeTal) is a highly water-soluble selenosugar with interesting antioxidant and skin-tissue-repair properties; it is highly stable in simulated gastric and gastrointestinal fluids and is a potential pharmaceutical ingredient that may be administered orally. Hepatic toxicity is often a major problem with novel drugs and can result in drug withdrawal from the market. Predicting hepatotoxicity is therefore essential to minimize late failure in the drug-discovery process. Herein, we report in vitro studies to evaluate the cytotoxic and genotoxic potential of SeTal in HepG2 and hepatocyte-like differentiated HepaRG cells. Except for extremely high concentrations (10 mM, 68 h-treatment in HepG2), SeTal did not affect the viability of each cell type. While the highest examined concentrations (0.75 and 1 mM in HepG2; 1 mM in HepaRG) were observed to induce primary DNA damage, SeTal did not exhibit clastogenic or aneugenic activity toward either HepG2 or HepaRG cells. Moreover, no significant cytostasis variations were observed in any experiment. The clearly negative results observed in the CBMN test suggest that SeTal might be used as a potential active pharmaceutical ingredient. The present study will be useful for the selection of non-toxic concentrations of SeTal in future investigations.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carl H. Schiesser reports a relationship with Seleno Therapeutics that includes: board membership. Michael J. Davies reports a relationship with Seleno Therapeutics that includes: board membership. Michael J. Davies and Carl H. Schiesser are major shareholders and Directors of Seleno Therapeutics, and are named as co-inventors on several patents of relevance to the work presented in this article. Michael J. Davies also declares commercial consultancy contracts with Novo Nordisk A/S. These funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish these results. The other authors declare no conflicts of interest with regard to the data presented.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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