A three-dimensional mouse liver organoid platform for assessing EDCs metabolites simulating liver metabolism

IF 10.3 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Environment International Pub Date : 2025-01-01 DOI:10.1016/j.envint.2024.109184
Ji Hyun Moon , Hyun-Soo Roh , Young Jae Park , Hyun Ho Song , Jieun Choi , Da Woon Jung , Soo Jin Park , Ho Jin Park , So-Hyeon Park , Da-Eun Kim , Gahee Kim , Joong-Hyuck Auh , Dong Ha Bhang , Hong Jin Lee , Do Yup Lee
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Abstract

Hepatic metabolism is an important process for evaluate the potential activity and toxicity of endocrine disrupting chemicals (EDCs) metabolites. Organization for Economic Co-operation and Development (OECD) has advocated the development of in vitro assays that mimic in vivo hepatic metabolism to eventually replace classical animal tests. In response to this need, we established a 3D mouse liver organoid (mLO) platform that mimics the animal model and is distinct from existing models. We evaluated the effects the activity of EDC metabolites generated through mLOs based on human cell-based reporter gene assays in addition to existing models. This study emphasizes the importance of hepatic ex-vivo and suggests the need a new metabolic model through a 3D mLOs platform. These results indicate that mLOs provides a novel biological method to screen for potential endocrine-disrupting activities of EDC metabolites.

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模拟肝脏代谢,评估EDCs代谢物的三维小鼠肝脏类器官平台
肝脏代谢是评价内分泌干扰物代谢产物潜在活性和毒性的重要过程。经济合作与发展组织(OECD)提倡发展模拟体内肝脏代谢的体外试验,以最终取代经典的动物试验。针对这一需求,我们建立了一个3D小鼠肝类器官(mLO)平台,该平台模仿动物模型,与现有模型有所不同。除了现有模型外,我们还基于人类细胞报告基因检测评估了mLOs产生的EDC代谢物活性的影响。本研究强调了肝脏离体代谢的重要性,并提出需要通过3D mLOs平台建立新的代谢模型。这些结果表明,mLOs为筛选EDC代谢物潜在的内分泌干扰活性提供了一种新的生物学方法。
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来源期刊
Environment International
Environment International 环境科学-环境科学
CiteScore
21.90
自引率
3.40%
发文量
734
审稿时长
2.8 months
期刊介绍: Environmental Health publishes manuscripts focusing on critical aspects of environmental and occupational medicine, including studies in toxicology and epidemiology, to illuminate the human health implications of exposure to environmental hazards. The journal adopts an open-access model and practices open peer review. It caters to scientists and practitioners across all environmental science domains, directly or indirectly impacting human health and well-being. With a commitment to enhancing the prevention of environmentally-related health risks, Environmental Health serves as a public health journal for the community and scientists engaged in matters of public health significance concerning the environment.
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