烯胺的活性会引起细胞毒性,并激活氧化应激反应
Julia Huchthausen1, Beate I Escher1,2, Nico Grasse3
1Department of Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstr. 15, 04318 Leipzig, Germany.
Chemical research in toxicology
|August 2, 2023
概括
烯胺是工业化学品,通过与生物分子的反应引起毒性. 它们与谷氨 (GSH) 的反应性与细胞毒性和氧化应激相关,与不太反应性的甲基烯胺不同.
科学领域:
- 毒理学 毒理学 毒理学
- 化学反应性 化学反应性
- 生物化学 生物化学
背景情况:
- 烯胺是广泛使用的工业化学品,已知对健康有不良影响,包括致癌性和神经毒性.
- 它们的毒性主要是由与DNA和蛋白质等生物核友的反应驱动的.
- 了解烯胺和甲烯胺之间的毒性差异对于风险评估至关重要.
研究的目的:
- 研究各种烯胺和甲烯胺的细胞毒性和氧化应激反应.
- 阐明化学反应性,特别是与谷氨 (GSH) 之间的关系和观察到的毒理效应.
- 为了区分烯胺与甲烯胺的毒理学机制.
主要方法:
- 评估了10 (甲基) 烯胺的细胞毒性和氧化应激反应,使用了三种10 (甲基) 烯胺的记者基因细胞系.
- 测量了与谷氨 (GSH) 反应的烯胺的二次降解速率常量 (kGSH).
- 使用液体色谱与高分辨率质谱相结合,以识别GSH合物.
主要成果:
- 烯胺呈现出高过量毒性,而甲烯胺则作为基线毒素起作用.
- 只有烯胺与GSH发生反应,反应速率各不相同 (例如,NMBA最高,NDA最低).
- 细胞毒性和氧化应激激活与烯胺反应速率常数与GSH线性相关.
结论:
- 烯胺与GSH的反应性是它们细胞毒性和氧化应激诱导的关键驱动因素.
- 反应性的差异归因于电子效应 (电荷密度,甲基组) 和硬质因素.
- GSH结合既是解毒途径,也是破坏细胞氧化还原平衡的机制.
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