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通过不可挽回的DNA损伤和自流阻塞引起的托森达宁诱导的肝损伤

Yifan Lin¹, Jian Zhang¹, Xinyue Gao²

¹Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, Fujian, China.

Phytomedicine : international journal of phytotherapy and phytopharmacology

|March 6, 2025

概括

托森丹尼 (TO) 是一种来自梅利亚托森丹果的化合物,通过损害DNA修复和自而导致肝损伤. 这导致无法修复的DNA损伤和细胞循环停止,突出显示TO.

科学领域:

毒理学毒理学毒理学
分子生物学分子生物学
药理学药理学是指药理学的学科.

背景情况:

梅利亚是西布的前任. 在Zucc. (MT) 水果传统上用于缓解疼痛和治疗圆虫.
图森达宁 (TO) 是MT中的关键生物活性化合物,但具有已知的肝毒性质.
了解TO的毒性机制对于其安全的临床应用至关重要.

研究的目的:

为了全面调查TO诱导肝毒性的毒性机制.
阐明DNA损伤,细胞循环停止和自失调在TO毒性的作用.
探索这些途径的协同效应.

主要方法:

用不同度的TO治疗了HepG2细胞和斑马鱼.
转录学和计算分子模拟 (网络药理学,分子对接,分子动力学) 用于目标预测.
机制验证涉及光探针,流式细胞计,qPCR和西部涂抹.

主要成果:

TO诱导了氧化应激,线粒体损伤,并抑制了DNA修复途径 (DNA依赖蛋白激酶催化子单元).
这导致了无法修复的DNA损伤和G1/S阶段细胞周期停止.
自流的干扰损害了受损器官的去除,加剧了损伤,导致肝细胞死亡.

结论:

TO损害了DNA损伤反应 (DDR) 和自,导致DNA损伤无法修复.
这会通过与环林蛋白和瘤抑制基因的相互作用来破坏细胞循环的进展.
这些综合作用对TO诱导的肝毒性有显著的贡献.

关键词:

细胞循环的细胞周期 DNA损伤反应的反应肝毒性肝毒性肝毒性图森达尼尼尼是什么意思

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