相关实验视频
Updated: Jul 6, 2025
07:58
Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury
Published on: July 17, 2016
8.9K
对毒性产生不良结果的途径网络的开发
D A Barnes1, J W Firman2, S J Belfield2
1Division of Pharmacology, Utrecht University, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
Archives of toxicology
|January 10, 2024
概括
不良结果途径 (AOPs) 网络模型毒性. 这项研究确定了线粒体功能障碍和氧化应激等关键事件,为化学安全评估的新非动物测试方法铺平了道路.
科学领域:
- 毒理学 毒理学 毒理学
- 计算生物学 计算生物学
- 生物化学 生物化学
背景情况:
- 负面结果途径 (AOPs) 提供了化学毒性机制的结构化,基于证据的表述.
- 线性AOP通常无法捕捉复杂的毒理过程,需要网络方法.
- AOP网络有助于理解化学相互作用,并在复杂的暴露场景中预测不良结果.
研究的目的:
- 通过连接13个个单独的AOP,开发一个针对毒性的不良结果途径 (AOP) 网络.
- 为了确定关键事件 (KEs) 中心的各种脏相关的不良结果.
- 建立一个开发体外和体内方法评估化学诱导毒性的基础.
主要方法:
- 利用已建立的标准,从AOP-Wiki数据库中构建一个AOP网络,专注于毒性.
- 分析了模拟的AOP网络的拓特征.
- 在网络中确定了中央和高度连接的关键事件 (KE).
主要成果:
- 成功开发了一个AOP网络,连接了13个与毒性相关的AOP.
- 确定了线粒体功能障碍,氧化应激和管状亡是最连接和中心的KEEs.
- 这些中心KE与诸如功能衰竭和慢性病等不良结果有关.
结论:
- 开发的AOP网络为了解化学诱导毒性提供了一个全面的模型.
- 像线粒体功能障碍和氧化应激这样的中央KEEs是进一步研究的关键目标.
- 这种网络方法支持开发新的体外和内测试,以取代对的毒性评估的动物试验.
相关概念视频
01:19Pharmacovigilance
835
Post-marketing surveillance is a critical component of pharmaceutical regulation, often uncovering unanticipated adverse drug reactions (ADRs) once a drug is widely used over an extended period.
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
835
01:11Renal Failure: Dose Adjustments
92
In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
92
01:26Toxic Reactions: Overview
978
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,...
978
01:10Nephrons
2.5K
The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma...
2.5K
02:26Protein Networks
4.0K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.0K
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
432
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
432