线粒体对阿里斯托拉克坦I的吸收对其毒性起着至关重要的作用
Yan Zhou1, Ruirui Cui2, Mingkang Zhang3
1The First Clinical Medical School of Lanzhou University, Lanzhou, China; Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou, China; Engineering Research Centre of Prevention and Control for Clinical Medication Risk, Gansu Province, China.
Toxicology letters
|March 1, 2024
概括
阿里斯托拉克坦I (ALI) 是阿里斯托洛基酸I的有毒代谢物,被线粒体选择性地吸收,导致线粒体功能障碍. 这一发现为预防阿里斯托洛希酸诱导的毒性提供了新的策略.
科学领域:
- 毒理学 毒理学 毒理学
- 线粒体生物学 线粒体生物学
- 细胞的新陈代谢
背景情况:
- 阿里斯托洛基酸I (AAI) 被代谢成阿里斯托拉克坦I (ALI),一种有毒化合物.
- 已知线粒体中脂友性子的积累,但ALI的线粒体吸收是不具特征的.
研究的目的:
- 研究ALI的细胞吸收和线粒体局部化.
- 为了确定ALI对线粒体功能的影响.
主要方法:
- 使用HK-2细胞和线粒体选择性染料进行细胞分布研究.
- 采用碳酸4- ((trifluoromethoxy) 化来评估线粒体膜的潜在影响.
- 监测ALI与有机离子载体 (OAT1/3) 的相互作用.
主要成果:
- ALI 快速透到 HK-2 细胞,独立于 OAT1/3.3.
- ALI的细胞分布反映了线粒体选择性染料的细胞分布.
- 线粒体膜脱极化抑制了ALI的吸收,这表明线粒体的选择性积累.
- ALI治疗导致观察到的线粒体功能障碍.
- 抑制OAT1/3可能会加剧ALI诱导的毒性.
结论:
- 阿里斯托拉克坦I被线粒体选择性地吸收.
- 这种ALI的线粒体积累导致功能障碍.
- 了解ALI的线粒体吸收提供了减轻AAI诱导毒性的见解.
相关概念视频
The Electron Transport Chain
16.7K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.7K
Carrier-Mediated Transport
422
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
422
Toxic Reactions: Overview
973
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,...
973
Drug Biotransformation: Overview
2.4K
Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
2.4K
ATP Synthase: Mechanism
14.6K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.6K
Enhanced Elimination of Poison
511
Poison can be effectively removed from the gastrointestinal (GI) tract through various decontamination procedures.
Antidotes serve a crucial role in counteracting the effects of poison by inhibiting enzymes responsible for producing harmful drug metabolites. In some cases, these toxic metabolites can be neutralized by endogenous cosubstrates, which are maintained at specific concentrations to prevent interaction with cellular macromolecules and subsequent cell death.
Renal excretion is the...
Antidotes serve a crucial role in counteracting the effects of poison by inhibiting enzymes responsible for producing harmful drug metabolites. In some cases, these toxic metabolites can be neutralized by endogenous cosubstrates, which are maintained at specific concentrations to prevent interaction with cellular macromolecules and subsequent cell death.
Renal excretion is the...
511


