• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

1,4-脱水-4-硒代-D-塔糖醇(SeTal)在人肝 HepG2 和 HepaRG 细胞中的遗传毒性评估。

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

机构信息

Department of Pharmaceutical Sciences (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy.

Seleno Therapeutics Pty. Ltd., Brighton East, Victoria 3187, Australia.

出版信息

Toxicology. 2023 Nov;499:153663. doi: 10.1016/j.tox.2023.153663. Epub 2023 Nov 2.

DOI:10.1016/j.tox.2023.153663
PMID:37924933
Abstract

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.

摘要

1,4-脱水-4-硒代-D-山梨醇(SeTal)是一种高度水溶性的硒代糖,具有有趣的抗氧化和皮肤组织修复特性;它在模拟胃液和胃肠道液中高度稳定,是一种具有潜在药用价值的成分,可能通过口服给药。新型药物通常会引起肝毒性,这可能导致药物从市场上撤出。因此,预测肝毒性对于最大限度地减少药物发现过程中的后期失败至关重要。在此,我们报告了体外研究,以评估 SeTal 在 HepG2 和肝样分化 HepaRG 细胞中的细胞毒性和遗传毒性潜力。除了极高的浓度(10 mM,68 h 在 HepG2 中处理)外,SeTal 不会影响每种细胞类型的活力。虽然观察到最高浓度(HepaRG 中的 0.75 和 1 mM;HepaRG 中的 1 mM)诱导原发性 DNA 损伤,但 SeTal 对 HepG2 或 HepaRG 细胞均没有表现出致裂或致畸活性。此外,在任何实验中均未观察到明显的细胞抑制变化。CBMN 试验中观察到的明显阴性结果表明,SeTal 可用作潜在的活性药物成分。本研究将有助于在未来的研究中选择无毒浓度的 SeTal。

相似文献

1
Genotoxicity assessment of 1,4-anhydro-4-seleno-D-talitol (SeTal) in human liver HepG2 and HepaRG cells.1,4-脱水-4-硒代-D-塔糖醇(SeTal)在人肝 HepG2 和 HepaRG 细胞中的遗传毒性评估。
Toxicology. 2023 Nov;499:153663. doi: 10.1016/j.tox.2023.153663. Epub 2023 Nov 2.
2
1,4-Anhydro-4-seleno-d-talitol (SeTal) protects endothelial function in the mouse aorta by scavenging superoxide radicals under conditions of acute oxidative stress.1,4-脱水-4-硒代-D-木糖醇(SeTal)在急性氧化应激条件下通过清除超氧阴离子自由基来保护小鼠主动脉的内皮功能。
Biochem Pharmacol. 2017 Mar 15;128:34-45. doi: 10.1016/j.bcp.2016.12.019. Epub 2016 Dec 24.
3
Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings.新型硒代糖(1,4-脱水-4-硒代-D-山梨醇,SeTal)对人冠状动脉细胞系和小鼠主动脉环的影响。
Biochem Pharmacol. 2020 Mar;173:113631. doi: 10.1016/j.bcp.2019.113631. Epub 2019 Sep 5.
4
Quantitative comparison of in vitro genotoxicity between metabolically competent HepaRG cells and HepG2 cells using the high-throughput high-content CometChip assay.采用高通量高内涵 CometChip 检测法对代谢能力较强的 HepaRG 细胞与 HepG2 细胞进行体外遗传毒性的定量比较。
Arch Toxicol. 2019 May;93(5):1433-1448. doi: 10.1007/s00204-019-02406-9. Epub 2019 Feb 21.
5
Contribution of ionic silver to genotoxic potential of nanosilver in human liver HepG2 and colon Caco2 cells evaluated by the cytokinesis-block micronucleus assay.通过胞质分裂阻滞微核试验评估离子银对纳米银在人肝癌HepG2细胞和结肠Caco2细胞中的遗传毒性潜力的贡献。
J Appl Toxicol. 2016 Apr;36(4):532-42. doi: 10.1002/jat.3279. Epub 2016 Jan 27.
6
Assessment of the genotoxic potential of indirect chemical mutagens in HepaRG cells by the comet and the cytokinesis-block micronucleus assays.应用彗星试验和胞质分裂阻断微核试验评估间接化学诱变剂在 HepaRG 细胞中的遗传毒性。
Mutagenesis. 2010 Nov;25(6):555-60. doi: 10.1093/mutage/geq039. Epub 2010 Jul 30.
7
Suppressive effect of 1,4-anhydro-4-seleno-D-talitol (SeTal) on atopic dermatitis-like skin lesions in mice through regulation of inflammatory mediators.1,4-脱水-4-硒代-D-山梨醇(SeTal)通过调节炎症介质对小鼠特应性皮炎样皮肤损伤的抑制作用。
J Trace Elem Med Biol. 2021 Sep;67:126795. doi: 10.1016/j.jtemb.2021.126795. Epub 2021 May 29.
8
Performance of HepaRG and HepG2 cells in the high-throughput micronucleus assay for in vitro genotoxicity assessment.HepaRG和HepG2细胞在用于体外遗传毒性评估的高通量微核试验中的表现。
J Toxicol Environ Health A. 2020 Nov 16;83(21-22):702-717. doi: 10.1080/15287394.2020.1822972. Epub 2020 Sep 27.
9
Use of HepG2 cell line for direct or indirect mutagens screening: comparative investigation between comet and micronucleus assays.利用HepG2细胞系进行直接或间接诱变剂筛选:彗星试验和微核试验的比较研究
Mutat Res. 2003 Apr 20;536(1-2):79-90. doi: 10.1016/s1383-5718(03)00031-7.
10
Treating atopic-dermatitis-like skin lesions in mice with gelatin-alginate films containing 1,4-anhydro-4-seleno-d-talitol (SeTal).用含有 1,4-脱水-4-硒代-D-苏糖醇(SeTal)的明胶-海藻酸盐膜治疗小鼠的特应性皮炎样皮肤损伤。
Int J Pharm. 2023 Jul 25;642:123174. doi: 10.1016/j.ijpharm.2023.123174. Epub 2023 Jun 25.

引用本文的文献

1
Exploring the Chemistry and Applications of Thio-, Seleno-, and Tellurosugars.硫代糖、硒代糖和碲代糖的化学及应用探索
Molecules. 2025 May 5;30(9):2053. doi: 10.3390/molecules30092053.