Loading...
Please wait, while we are loading the content...
Similar Documents
In vitro toxicological assessment of PhSeZnCl in human liver cells.
| Content Provider | Europe PMC |
|---|---|
| Author | di Vito, Raffaella Levorato, Sara Fatigoni, Cristina Acito, Mattia Sancineto, Luca Traina, Giovanna Villarini, Milena Santi, Claudio Moretti, Massimo |
| Abstract | Phenylselenenylzinc chloride (PhSeZnCl) is an air-stable selenolate, easily synthesizable through oxidative insertion of elemental zinc into the Se-halogen bond of the commercially available phenylselenyl chloride. PhSeZnCl was shown to possess a marked GPx-like activity both in NMR and in vitro tests, and to effectively react with cellular thiols, and was supposed for a potential use in the chemotherapy of drug-resistant cancers. However, activity of PhSeZnCl in hepatic cells has never been tested before now. In this in vitro approach, we evaluated the cytotoxic, genotoxic, and apoptotic activities, as well as the effects on cell cycle of PhSeZnCl in two preclinical hepatic models, namely HepG2 and HepaRG cells. Results showed that cell viability of HepG2 and HepaRG cells decreased in a dose-dependent manner, with a more marked effect in HepG2 tumour cells. Moreover, treatment with 50 µg/mL PhSeZnCl caused an increase of primary DNA damage (4 h) and a statistically significant increase of HepG2 cells arrested in G2/M phase. In addition, it altered mitochondrial membrane potential and induced chromosomal DNA fragmentation (24 h). In HepaRG cells, PhSeZnCl was able to determine a cell cycle-independent induction of apoptosis. Particularly, 50 µg/mL induced mitochondrial membrane depolarization after 24 h and apoptosis after 4 h treatment. Futhermore, all PhSeZnCl concentrations tested determined a significant increase of apoptotic cells after 24 h. Apoptosis was also highlighted by the detection of active Caspase-3 by Western Blot analysis after 24 h exposure. In conclusion, this first toxicological assessment provides new insights into the biological activity of PhSeZnCl in preclinical hepatic models that will be useful in future safety assessment investigation of this compound as a potential pharmaceutical.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43188-022-00148-y. |
| Related Links | https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9839901&blobtype=pdf |
| ISSN | 19768257 |
| Journal | Toxicological Research [Toxicol Res] |
| Volume Number | 39 |
| DOI | 10.1007/s43188-022-00148-y |
| PubMed Central reference number | PMC9839901 |
| Issue Number | 1 |
| PubMed reference number | 36721677 |
| e-ISSN | 22342753 |
| Language | English |
| Publisher | Springer Nature Singapore |
| Publisher Date | 2022-09-08 |
| Publisher Place | Singapore |
| Access Restriction | Open |
| Rights License | Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2022 |
| Subject Keyword | Phenylselenenylzinc chloride HepG2 HepaRG Comet assay Apoptosis Cell cycle |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Toxicology |
