测绘生理学:一种系统生物学方法,用于开发毒理学中的替代方法
Bernard Staumont1, Luiz Ladeira1, Alessio Gamba1
1Biomechanics Research Unit, GIGA Molecular and Computational Biology, University of Liège, Liège, Belgium.
ALTEX
|February 7, 2025
概括
生理地图 (PMs) 为化学安全提供了详细的机制性见解,支持开发与人类相关的新方法方法 (NAMs). 这种方法提高了毒理学预测,并减少了对动物试验的依赖.
科学领域:
- 毒理学 毒理学 毒理学
- 系统生物学 系统生物学
- 计算生物学 计算生物学
背景情况:
- 目前的化学品安全评估主要依赖于动物试验,这引发了伦理问题和有限的人类相关性.
- 无毒理学缺乏强大的生物机制基础,阻碍了准确的化学效应预测.
- 像不良结果途径 (AOPs) 这样的现有框架需要更详细的基因和细胞水平机制性见解.
研究的目的:
- 介绍生理地图 (PMs) 作为一种用于可视化器官功能中的生化过程的新工具.
- 通过系统生物学图形符号 (SBGN) 和受控的词汇库来实现可复制性的PM标准化.
- 提高基因和细胞层面的机制性理解,以支持新方法方法 (NAMs).
主要方法:
- 由疾病地图项目启发开发PM,代表生物化学途径.
- 应用系统生物学图形符号 (SBGN) 用于标准化和控制的词汇.
- 建立了策划指南,并强调了领域专家和策展人之间的合作.
主要成果:
- 创建了 (病理) 生理学的用户友好,标准化的可视化.
- PMs提供了详细的机制信息,补充了AOP开发.
- 促进了 in vitro 试验电池和 in silico 毒性模型的开发.
结论:
- PMs提供了一种标准化的方法来可视化和分析复杂的生物数据.
- 总理们加强了对开发与人类相关的NAM至关重要的机制理解.
- 毒理学和系统生物学之间的合作对于推进下一代风险评估至关重要.
相关概念视频
Toxic Reactions: Overview
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,...
Model Approaches for Pharmacokinetic Data: Physiological Models
Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...
Pharmacokinetic Models: Comparison and Selection Criterion
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Bioactivation and Tissue Toxicity
Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Toxicokinetics: Overview
Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...
Toxicity Testing in Animals
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...


