多个内源性化物放大了乙氨基诱导的肝损伤
Hong Pan1, Qi Luo1, Qiuyi Jing1
1Key Laboratory of Basic Pharmacology of Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi, 563003, China.
Chemico-biological interactions
|June 25, 2025
概括
乙氨基 (APAP) 导致肝损伤,部分是通过内源性化物来改变蛋白质. 阿尔德脱酶-2激活减少了这种损伤,为APAP肝毒性提供了新的治疗点.
科学领域:
- 生物化学 生物化学
- 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:
- 乙氨基 (APAP) 过量服用是导致急性肝损伤的主要原因.
- APAP诱导的肝毒性的确切机制尚未完全理解.
- 内源性化物可能在APAP肝损伤中发挥作用.
研究的目的:
- 为了研究内源性化物在APAP诱导的肝损伤中的作用.
- 在APAP注射后,在肝脏中识别阿尔德海德蛋白添加物.
- 探索针对化物修饰的治疗策略.
主要方法:
- 在APAP后的小鼠肝脏中识别自由生物性化物.
- 阿尔代-蛋白质添加物的量化.
- 抑制APAP的代谢激活 (CYP2E1抑制剂) 和阿尔代脱酶-2激活 (Alda-1).
主要成果:
- 发现了74种化物,47种形成的蛋白质添加物,29种新的肝脏.
- 阿尔代-蛋白质添加物在APAP后2-3小时达到峰值.
- 抑制APAP代谢和激活阿尔德海德脱酶-2可以减少添加物和肝损伤.
结论:
- 内源性化物通过添加剂共价蛋白修饰放大APAP肝损伤.
- 化物通过内在的毒性和JNK酸化导致肝毒性.
- 向aldehyde通路为APAP过量治疗提供了一种新的治疗方法.
相关概念视频
Phase II Reactions: Acetylation Reactions
381
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
381
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
397
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...
397
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
343
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...
343
Acetals and Thioacetals as Protecting Groups for Aldehydes and Ketones
4.6K
Acetals are formed by reacting two equivalents of alcohol with carbonyl compounds like aldehydes or ketones. Acetals are unaffected by bases, nucleophiles, oxidizing agents, and reducing agents. They serve as protecting groups for aldehydes and ketones. Acetals can be easily formed and also easily removed via mild acid hydrolysis.
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals...
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals...
4.6K
Oxidations of Aldehydes and Ketones to Carboxylic Acids
4.2K
Oxidation of aldehydes and ketones results in the formation of carboxylic acids. Aldehydes, bearing hydrogen next to the carbonyl group, are easily oxidized compared to ketones. This is because an aldehydic proton can easily be abstracted during oxidation.
Aldehydes readily undergo oxidation in strong oxidizing agents such as potassium permanganate and chromic acid. The oxidation can also be carried out using mild oxidizing agents such as silver oxide. In fact, aldehydes can be easily oxidized...
Aldehydes readily undergo oxidation in strong oxidizing agents such as potassium permanganate and chromic acid. The oxidation can also be carried out using mild oxidizing agents such as silver oxide. In fact, aldehydes can be easily oxidized...
4.2K
Toxic Reactions: Overview
1.2K
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
1.2K


