Nrf2作为乙氨基肝毒性的治疗点:对硫福拉进行的病例研究
Yasaman Etemadi1, Jephte Y Akakpo1, Anup Ramachandran1
1Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, USA.
Journal of biochemical and molecular toxicology
|August 20, 2023
概括
治疗性激活核因素红色素2相关因子2 (Nrf2) 并不是对乙氨基过量服用的可行治疗方法. 像硫福拉这样的Nrf2激活剂的保护性低于N-乙半氨酸.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
背景情况:
- 过量服用乙氨基 (APAP) 会导致严重的肝损伤和急性肝衰竭.
- N-乙半氨酸 (NAC) 是唯一批准的抗毒剂,但其治疗窗口很窄.
- 核因素红色素2相关因子2 (Nrf2) 激活是APAP肝毒性的潜在治疗标.
研究的目的:
- 评估Nrf2激活在治疗APAP诱导的肝损伤方面的治疗潜力.
- 评估短期Nrf2激活剂治疗是否在药物过量时在临床上可行.
主要方法:
- 使用了一种APAP肝毒性的小鼠模型.
- Nrf2激活剂硫福拉 (SFN) 在APAP后被使用.
- 评估了nrf2激活,基因表达和肝损伤标志物.
- 将SFN疗效与NAC治疗进行了比较.
主要成果:
- 短期SFN治疗 (≤3小时) 没有激活Nrf2或其向基因.
- 用SFN进行后期治疗显示,在6小时后,部分保护,与血红素氧酶-1激活有关.
- 与SFN相比,NAC在24小时内提供了优越和持续的保护.
结论:
- Nrf2激活器需要细胞应激才能激活,并表现出延迟的适应反应.
- 这些特征限制了它们在急性情况下的持续疗效,例如APAP过量服用.
- 与NAC相比,Nrf2激活剂对治疗APAP肝毒性不太适合.
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