马特林破坏Nrf2/GPX4抗氧化系统,并促进肝细胞铁化
Xi Wang1, Wenjing Zhu1, Miao Xing1
1School of Medicine, Yichun University, 576 XueFu Road, Yuanzhou District, Yichun, 336000, PR China.
Chemico-biological interactions
|September 16, 2023
概括
马特林通过诱导氧化应激相关的细胞死亡途径铁亡,导致肝损伤. 抑制铁或增强抗氧化剂防御可以防止这种毒性.
科学领域:
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 马特林 (MT) 是来自Sophora flavescens的类化合物,具有多种生物活性,但引起了临床毒性问题.
- 了解Matrine诱导的肝损伤机制对于安全的临床应用至关重要.
研究的目的:
- 为了研究铁死在马特林诱导的肝损伤中的作用.
- 阐明涉及抗氧化途径和铁平衡的潜在机制.
主要方法:
- 评估肝脏组织的病理变化和L02细胞活力.
- 测量氧化应激标志物 (SOD,GSH,MDA,ROS) 和脂质过氧化水平.
- 分析关键铁与相关因素 (FTH,Nrf2,xCT,GPX4,HO-1,FSP1,TRF1,DMT1) 的铁稳定和蛋白质表达.
- 评估铁灭菌抑制剂,Nrf2激动剂和补充剂的保护作用.
主要成果:
- 马特林诱导了肝脏组织的显著损伤,并降低了L02细胞活力.
- 马特林破坏了抗氧化剂平衡,增加了氧化应激和脂质过氧化,表明铁.
- 马特林改变了铁的稳定性和调节了与铁死相关的关键蛋白质水平,包括对Nrf2/GPX4抗氧化系统的下调.
- 铁酶抑制剂,Nrf2激动剂和补充剂减轻了Matrine的细胞毒性作用.
结论:
- 马特林通过抑制Nrf2/GPX4抗氧化系统来触发肝细胞铁.
- 向铁亡途径为Matrine诱导的肝毒性提供了潜在的治疗策略.
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