乙酸通过促进Nrf2/GPX4介导的铁灭菌诱导毒性
Haiyan Zhu1, Yenan Duan1, Yijing Yang1
1School of Medicine, Yichun University, 576 XueFu Road, Yuanzhou District, Yichun, 336000, PR China.
Chemico-biological interactions
|February 16, 2024
概括
酸 (SA) 通过诱导细胞死亡的一种形式铁亡,导致损伤. 保护铁或激活Nrf2/GPX4通路可以防止这种SA诱导的毒性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 从Aesculus wilsonii Rehd种子中提取的aescinate (SA) 是临床上使用的,但与包括功能障碍在内的不良事件增加有关.
- 在SA诱导的毒性背后的精确机制仍然不完全理解,需要进一步调查其毒性作用.
研究的目的:
- 研究酸盐 (SA) 对损伤的毒性作用和阐明病原性机制.
- 确定铁和Nrf2/GPX4通路在SA诱导的毒性中的作用.
主要方法:
- 评估功能标志物 (BUN,Scr,Kim-1) 和组织病理反应的SA.
- 使用NRK-52E细胞进行体外研究,以评估SA诱导的细胞死亡和膜完整性.
- 对参与铁代谢,氧化应激和铁的关键蛋白质和分子水平的分析 (FTH,Nrf2,xCT,GPX4,FSP1,TFR1,ACSL4,GSH,Cys,Fe2+,MDA,ROS).
主要成果:
- SA显著提高了BUN,Scr和Kim-1水平,可以观察到脏组织的病理变化.
- SA诱导了NRK-52E细胞死亡,破坏了细胞膜的完整性,并改变了调节铁和氧化应激的蛋白质水平.
- SA降低了保护分子 (Nrf2,GPX4,GSH),同时增加了亲氧化和细胞死亡标志物,导致铁亡和氧化损伤.
结论:
- 酸 (SA) 通过抑制Nrf2/GPX4信号通路,通过氧化损伤和铁亡诱导毒性.
- 抑制ferroptosis或激活Nrf2/GPX4通路有效地减轻SA诱导的损伤,突出潜在的治疗标.
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