Haloacetamides 消毒副产品,这是非酒精性脂肪肝疾病的潜在危险因素
Zhiqiang Jiang1, Lili Yang1, Qinxin Liu1
1Center for Water and Health, Key Laboratory of the Public Health Safety, Ministry of Education, Department of Environmental Health, School of Public Health, Fudan University Shanghai, 200032, China.
Water research
|June 30, 2024
概括
饮用水中的乙胺 (HAcAms) 通过引起脂质积累和肝细胞损伤,导致非酒精性脂肪性肝病 (NAFLD). 这通过氧化应激和特定细胞通路的激活而发生.
科学领域:
- 环境健康 环境健康
- 肝病学 肝病学是一种肝病学.
- 毒理学 毒理学 毒理学
背景情况:
- 非酒精性脂肪肝疾病 (NAFLD) 涉及异常的脂质沉积,并与氧化应激相关.
- 乙胺 (HAcAms) 是不受管制的饮用水消毒副产品,是NAFLD的潜在贡献者.
- 氧化应激在NAFLD的发病和进展中发挥着作用.
研究的目的:
- 研究HAcAms对人类肝细胞 (LO-2) 中的脂质代谢的影响.
- 探索HAcAms诱导的脂质积累和肝细胞损伤的潜在机制,重点关注NRF2通路.
主要方法:
- 正常和NRF2-knockdown (NRF2-KD) LO-2细胞暴露于不同度的HAcAms.
- 使用CRISPR/Cas9技术创建NRF2-KD细胞系.
- 评估了脂质沉积,甘油三积累,新生脂质生成和铁.
主要成果:
- 高度的HAcAms诱导了LO-2细胞中显著的脂质沉积和甘油三积累.
- HAcAms激活了NRF2/PPARγ通路,导致肝细胞脂质积累.
- HAcAms通过诱导铁亡,特别是在NRF2-KD细胞中,加剧了肝细胞毒性.
结论:
- HAcAms被确定为NAFLD发展的重要风险因素.
- NRF2/PPARγ通路和铁亡是HAcAms诱导的肝损伤的关键机制.
- 需要进一步的基于人口的研究来确认HAcAms对NAFLD的影响.
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