将动物和体外肺细胞模型中的炎症关键事件统一起来的当前挑战。

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Chemical Research in Toxicology Pub Date : 2024-10-21 Epub Date: 2024-08-08 DOI:10.1021/acs.chemrestox.4c00113
Isidora Loncarevic, Seyran Mutlu, Martina Dzepic, Sandeep Keshavan, Alke Petri-Fink, Fabian Blank, Barbara Rothen-Rutishauser
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引用次数: 0

摘要

每年都有大量新颖的体外模型出现,以减少或取代动物试验,因此迫切需要采用体外-体内外推法(IVIVE)对这些系统进行设计、协调和验证。特别是在吸入毒理学方面,目前缺乏可有效替代动物试验的预测性和流行的体外肺模型。通过应用 "不良后果途径"(AOP)框架,可提高此类模型的预测能力,该框架将与 IVIVE 相关的关键事件(KE)随机联系起来。然而,目前发现的困难之一是,针对特定毒物的体外和动物模型的终点分析和特定检测的读数并不统一,这使得调整工作具有挑战性。我们总结了这两个系统中终点分析的当前技术水平,重点关注炎症诱导效应,并为未来的研究方向提供指导,以提高一致性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Current Challenges to Align Inflammatory Key Events in Animals and Lung Cell Models <i>In Vitro</i>.

Current Challenges to Align Inflammatory Key Events in Animals and Lung Cell Models In Vitro.

With numerous novel and innovative in vitro models emerging every year to reduce or replace animal testing, there is an urgent need to align the design, harmonization, and validation of such systems using in vitro-in vivo extrapolation (IVIVE) approaches. In particular, in inhalation toxicology, there is a lack of predictive and prevalidated in vitro lung models that can be considered a valid alternative for animal testing. The predictive power of such models can be enhanced by applying the Adverse Outcome Pathways (AOP) framework, which casually links key events (KE) relevant to IVIVE. However, one of the difficulties identified is that the endpoint analysis and readouts of specific assays in in vitro and animal models for specific toxicants are currently not harmonized, making the alignment challenging. We summarize the current state of the art in endpoint analysis in the two systems, focusing on inflammatory-induced effects and providing guidance for future research directions to improve the alignment.

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来源期刊
CiteScore
7.90
自引率
7.30%
发文量
215
审稿时长
3.5 months
期刊介绍: Chemical Research in Toxicology publishes Articles, Rapid Reports, Chemical Profiles, Reviews, Perspectives, Letters to the Editor, and ToxWatch on a wide range of topics in Toxicology that inform a chemical and molecular understanding and capacity to predict biological outcomes on the basis of structures and processes. The overarching goal of activities reported in the Journal are to provide knowledge and innovative approaches needed to promote intelligent solutions for human safety and ecosystem preservation. The journal emphasizes insight concerning mechanisms of toxicity over phenomenological observations. It upholds rigorous chemical, physical and mathematical standards for characterization and application of modern techniques.
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