甲基双酸盐通过调节氧化压力相关基因来改善四化碳诱导的肝损伤
Rong Wang1,2,3, Huanhuan Shen1, Jiaxiang Zhang1
1Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai 264003, China.
Molecules (Basel, Switzerland)
|December 23, 2023
概括
丁甲基双酸盐 (DMB) 在保护由四化碳 (CCl4) 引起的肝损伤方面表现有前途. 这种新型化合物减轻了氧化应激,并改善了大鼠肝功能关键标志物.
科学领域:
- 生物化学 生物化学
- 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:
- 肝病是一个全球性的健康负担,每年导致数百万人的死亡.
- 碳四化物 (CCl4) 是一种常见的毒素,用于诱导实验性肝损伤.
- 氧化应激在肝损伤的病原发生中起着至关重要的作用.
研究的目的:
- 合成和评估新型化合物二甲基双酸盐 (DMB) 对CCl4诱导的肝损伤的保护作用.
- 研究DMB的作用机制,重点关注与氧化压力相关基因的调节.
主要方法:
- 使用光谱和质谱学合成和结构确认DMB.
- 将DMB给CCl4治疗的老鼠,并测量肝损伤生物标志物 (ALT,AST,DBIL,TBIL,ALP,LDH).
- 活性氧物种 (ROS) 和氧化应激标志物 (GSH,MDA) 的 in vitro 和 in vivo 评估.
- 分析与亡 (P53,Bax,BCl2) 和氧化应激反应 (Nrf2,GCLC) 相关的基因和蛋白质表达.
主要成果:
- 在剂量上,DMB显著降低了肝酶 (ALT,AST,DBIL,TBIL,ALP,LDH) 的升高水平,与西利马林相似.
- 治疗DMB降低了ROS和MDA水平,同时增加了CCl4暴露细胞和老鼠肝组织中的GSH,Nrf2和GCLC含量.
- DMB调节了与亡相关的蛋白质,降低了P53和Bax的表达,增加了Bcl2的表达.
结论:
- 丁甲基双酸盐 (DMB) 对CCl4诱导的肝损伤具有显著的肝保护作用.
- DMB通过减轻氧化应激和调节亡途径来改善肝损伤.
- DMB代表了与氧化应激相关的肝脏疾病的潜在治疗剂.
相关概念视频
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
205
Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
205
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
215
Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
215


