在实验室中,八种天然阿里斯托拉克坦的毒性和结构毒性关系
Shiyu Xue1, Weilian Bao1, Jiaren Lyu1
1Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai, 201203, China.
Toxicon : official journal of the International Society on Toxinology
|December 14, 2024
概括
在人类细胞中,八种天然的亚里斯托拉克坦 (ALs) 显示出不同程度的毒性. 特定的化学结构,如甲基二氧化和甲基基团,增加ALs.
科学领域:
- 毒理学 毒理学 毒理学
- 自然产品 化学 化学
- 细胞生物学 细胞生物学
背景情况:
- 阿里斯托拉克坦 (ALs) 和阿里斯托洛希克酸 (AAs) 之间的结构相似性引发了安全问题.
- 自然AL比AAs更广泛,增加了暴露风险.
- 了解ALs的毒性对公共健康至关重要.
研究的目的:
- 在人管状上皮细胞 (HK-2细胞) 上评估和比较8种天然AL的体外毒性.
- 调查ALS的结构毒性关系.
- 评估ALS的化学结构及其对损伤标志物和氧化应激的影响之间的相关性.
主要方法:
- 人类管状上皮细胞 (HK-2) 暴露于八种天然的ALS.
- 用MTT试验评估细胞活力,以确定IC50值.
- 用ELISA测量损伤分子-1 (KIM-1),转化生长因子-β1 (TGF-β1) 和纤维素 (FN) 的水平.
- 细胞内活性氧物种 (ROS) 水平使用ROS测定检测.
主要成果:
- 所有八个AL都对HK-2细胞表现出特定的毒性.
- 亚里斯托拉克坦I (AL I),AL BII和韦鲁胺表现出最强大的细胞毒性 (IC50 = 2.492.78 μM).
- 甲基二氧化和甲基组增强了AL的毒性,而氧和N-甲基组降低了它.
- ALs以剂量依赖的方式增加了KIM-1水平和ROS生成,与细胞毒性相关.
- 四种最有毒的ALS通过提高TGF-β1和FN水平诱导纤维化.
结论:
- 天然ALs在体外具有显著的毒性,根据它们的化学结构有不同的效力.
- 氨酸和胺环上的特定功能组极大地影响了ALS对细胞的毒性作用.
- ALS可以通过氧化应激和纤维化标志物的上调调节诱导损伤和纤维化,突出显示潜在的健康风险.
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