回顾肝脏纳米毒理学-总结最近的发现和下一代研究设计的考虑。

IF 6.4 2区 医学 Q1 ENVIRONMENTAL SCIENCES Journal of Toxicology and Environmental Health-Part B-Critical Reviews Pub Date : 2020-05-18 Epub Date: 2020-04-23 DOI:10.1080/10937404.2020.1751756
Ali Kermanizadeh, Leagh G Powell, Vicki Stone
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引用次数: 24

摘要

肝脏是人体最重要的多功能器官之一。在各种关键功能中,它是主要的解毒中心,主要涉及清除可能包括到达该器官的颗粒的外来生物。现在已经确定,大量注射、摄入或吸入的纳米材料(NMs)从主要暴露部位转移并在肝脏中积累。本文旨在总结和讨论肝脏纳米毒理学领域的进展,并重点强调仍然存在的知识空白。体内研究清楚地表明,低溶解度NMs主要积聚在肝巨噬细胞Kupffer细胞(KC)中,而不是肝细胞中。衬在肝窦内的KCs是体内第一个与NMs接触的细胞类型。此外,这些巨噬细胞控制着健康肝脏的整体炎症反应。因此,NM与KCs在体外的相互作用显得非常重要。许多急性体内研究证明了多种NMs诱导的毒性迹象。然而,由于肝脏独特而无与伦比的再生能力,急性研究可能没有那么有意义。在几乎所有包括恢复期的调查中,健康的肝脏能够从NM挑战中恢复。这个器官的再生能力在体外是无法复制的。然而,建议和证据提供了更多的生理相关的体外模型的设计。肝脏疾病模型增强纳米颗粒诱导的肝毒性。该综述为未来肝脏纳米毒理学研究设计提供了一些重要建议。这是非常重要的,因为它的发现是高度相关的,因为更先进的体外和计算机模型的发展,旨在改善生理学相关的毒理学测试策略和弥合体外和体内实验之间的差距。
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A review of hepatic nanotoxicology - summation of recent findings and considerations for the next generation of study designs.

The liver is one of the most important multi-functional organs in the human body. Amongst various crucial functions, it is the main detoxification center and predominantly implicated in the clearance of xenobiotics potentially including particulates that reach this organ. It is now well established that a significant quantity of injected, ingested or inhaled nanomaterials (NMs) translocate from primary exposure sites and accumulate in liver. This review aimed to summarize and discuss the progress made in the field of hepatic nanotoxicology, and crucially highlight knowledge gaps that still exist.Key considerations include In vivo studies clearly demonstrate that low-solubility NMs predominantly accumulate in the liver macrophages the Kupffer cells (KC), rather than hepatocytes.KCs lining the liver sinusoids are the first cell type that comes in contact with NMs in vivo. Further, these macrophages govern overall inflammatory responses in a healthy liver. Therefore, interaction with of NM with KCs in vitro appears to be very important.Many acute in vivo studies demonstrated signs of toxicity induced by a variety of NMs. However, acute studies may not be that meaningful due to liver's unique and unparalleled ability to regenerate. In almost all investigations where a recovery period was included, the healthy liver was able to recover from NM challenge. This organ's ability to regenerate cannot be reproduced in vitro. However, recommendations and evidence is offered for the design of more physiologically relevant in vitro models.Models of hepatic disease enhance the NM-induced hepatotoxicity.The review offers a number of important suggestions for the future of hepatic nanotoxicology study design. This is of great significance as its findings are highly relevant due to the development of more advanced in vitro, and in silico models aiming to improve physiologically relevant toxicological testing strategies and bridging the gap between in vitro and in vivo experimentation.

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来源期刊
CiteScore
13.80
自引率
6.90%
发文量
13
审稿时长
>24 weeks
期刊介绍: "Journal of Toxicology and Environmental Health: Part B - Critical Reviews" is an academic journal published by Taylor & Francis, focusing on the critical examination of research in the areas of environmental exposure and population health. With an ISSN identifier of 1093-7404, this journal has established itself as a significant source of scholarly content in the field of toxicology and environmental health. Since its inception, the journal has published over 424 articles that have garnered 35,097 citations, reflecting its impact and relevance in the scientific community. Known for its comprehensive reviews, the journal also goes by the names "Critical Reviews" and "Journal of Toxicology & Environmental Health, Part B, Critical Reviews." The journal's mission is to provide a platform for in-depth analysis and critical discussion of the latest findings in toxicology, environmental health, and related disciplines. By doing so, it contributes to the advancement of knowledge and understanding of the complex interactions between environmental factors and human health, aiding in the development of strategies to protect and improve public health.
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