{"title":"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。","authors":"Ali Kermanizadeh, Leagh G Powell, Vicki Stone","doi":"10.1080/10937404.2020.1751756","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>In vivo</i> 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 <i>in vivo</i>. Further, these macrophages govern overall inflammatory responses in a healthy liver. Therefore, interaction with of NM with KCs <i>in vitro</i> appears to be very important.Many acute <i>in vivo</i> 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 <i>in vitro</i>. However, recommendations and evidence is offered for the design of more physiologically relevant <i>in vitro</i> 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 <i>in vitro</i>, and <i>in silico</i> models aiming to improve physiologically relevant toxicological testing strategies and bridging the gap between <i>in vitro</i> and <i>in vivo</i> experimentation.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2020-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10937404.2020.1751756","citationCount":"24","resultStr":"{\"title\":\"A review of hepatic nanotoxicology - summation of recent findings and considerations for the next generation of study designs.\",\"authors\":\"Ali Kermanizadeh, Leagh G Powell, Vicki Stone\",\"doi\":\"10.1080/10937404.2020.1751756\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>In vivo</i> 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 <i>in vivo</i>. Further, these macrophages govern overall inflammatory responses in a healthy liver. Therefore, interaction with of NM with KCs <i>in vitro</i> appears to be very important.Many acute <i>in vivo</i> 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 <i>in vitro</i>. However, recommendations and evidence is offered for the design of more physiologically relevant <i>in vitro</i> 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. 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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.
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.