在斑马鱼幼虫中,N-nitrosodin-propylamine的肝毒性通过上调Wnt途径来提高
Ying Wang1, Shouqiang Huang2, Dagang Wang2
1Center for Clinical Medicine Research, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China; College of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, Guangdong Province, China.
Toxicology and applied pharmacology
|October 31, 2024
概括
通过增加氧化应激,亡和Wnt信号传递,N-尼托索丁-胺在斑马鱼中引起肝毒性. 阿斯塔克桑和IWR-1治疗可以防止这些影响.
科学领域:
- 环境毒理学环境毒理学
- 发育生物学是发展生物学.
- 肝毒性研究 肝毒性研究
背景情况:
- N-尼托索丁-胺是一种有机化合物,具有潜在的环境风险.
- 意外释放可能导致水污染.
- 它对发育的毒性,特别是对肝脏的毒性,以前没有在斑马鱼中进行研究.
研究的目的:
- 调查斑马鱼中N-尼托罗斯-胺的发育毒性.
- 阐明N-尼托罗斯-胺诱导的肝毒性潜在机制.
- 为了评估潜在的防护剂对这种毒性.
主要方法:
- 斑马鱼幼虫从受精后72小时 (hpf) 开始暴露在N-nitrosodin-propylamine中.
- 评估了包括死亡率,生长和肝脏形态在内的毒性反应.
- 分析了涉及氧化应激,亡和Wnt信号通路基因表达的机制.
主要成果:
- 暴露导致死亡率增加,黄囊吸收延迟,体长缩短和肝脏形态异常.
- 肝毒性与氧化应激升高,肝细胞亡增加和Wnt信号调节升高有关.
- 阿斯塔克桑丁和IWR-1证明了对N-尼托罗斯-烯胺诱导的肝损伤的保护作用.
结论:
- 在斑马鱼中,N-nitrosodin-propylamine通过Wnt信号通路的上调调节,氧化应激和亡诱导发育性肝毒性.
- 斑马鱼模型对于评估环境污染物的毒性是有效的.
- 阿斯塔克桑丁和IWR-1显示出作为潜在的治疗干预措施的希望.
相关概念视频
01:202° Amines to N-Nitrosamines: Reaction with NaNO2
Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
01:26Physical Properties of Amines
Amines with low molecular weight are usually gaseous at room temperature, while those with high molecular weight are liquid or solids in nature. Usually, low molecular weight amines have a rotten fish-like smell. Diamines typically have a pungent smell. For instance, cadaverine and putrescine, depicted in Figure 1, are two molecules responsible for decaying tissue.