Kermanizadeh Ali, Løhr Mille, Roursgaard Martin, Messner Simon, Gunness Patrina, Kelm Jens M, Møller Peter, Stone Vicki, Loft Steffen
Department of Public Health, University of Copenhagen, Section of Environmental Health, Copenhagen, 1014, Denmark.
Heriot Watt University, School of Life Sciences, Nanosafety research group, Edinburgh, EH14 4AS, UK.
Part Fibre Toxicol. 2014 Oct 20;11:56. doi: 10.1186/s12989-014-0056-2.
The liver has a crucial role in metabolic homeostasis as well as being the principal detoxification centre of the body, removing xenobiotics and waste products which could potentially include some nanomaterials (NM). With the ever increasing public and occupational exposure associated with accumulative production of nanomaterials, there is an urgent need to consider the possibility of detrimental health consequences of engineered NM exposure. It has been shown that exposure via inhalation, intratracheal instillation or ingestion can result in NM translocation to the liver. Traditional in vitro or ex vivo hepatic nanotoxicology models are often limiting and/or troublesome (i.e. reduced metabolism enzymes, lacking important cell populations, unstable with very high variability, etc.).
In order to rectify these issues and for the very first time we have utilised a 3D human liver microtissue model to investigate the toxicological effects associated with a single or multiple exposure of a panel of engineered NMs (Ag, ZnO, MWCNT and a positively charged TiO₂).
Here we demonstrate that the repeated exposure of the NMs is more damaging to the liver tissue as in comparison to a single exposure with the adverse effects more significant following treatment with the Ag and ZnO as compared with the TiO₂ and MWCNT NMs (in terms of cytotoxicity, cytokine secretion, lipid peroxidation and genotoxicity).
Overall, this study demonstrates that the human microtissue model utilised herein is an excellent candidate for replacement of traditional in vitro single cell hepatic models and further progression of liver nanotoxicology.
肝脏在代谢稳态中起着关键作用，同时也是人体主要的解毒中心，可清除可能包括一些纳米材料（NM）的外源性物质和废物。随着纳米材料产量的不断增加，公众和职业接触纳米材料的情况日益增多，迫切需要考虑工程纳米材料暴露对健康产生有害影响的可能性。研究表明，通过吸入、气管内滴注或摄入纳米材料可导致其向肝脏转移。传统的体外或离体肝脏纳米毒理学模型往往存在局限性和/或麻烦之处（例如代谢酶减少、缺乏重要细胞群体、稳定性差且变异性很高等）。
为了纠正这些问题，我们首次利用三维人体肝脏微组织模型来研究一组工程纳米材料（银、氧化锌、多壁碳纳米管和带正电荷的二氧化钛）单次或多次暴露相关的毒理学效应。
我们在此证明，与单次暴露相比，纳米材料的重复暴露对肝脏组织的损害更大，与二氧化钛和多壁碳纳米管纳米材料相比，用银和氧化锌处理后产生的不良反应更显著（在细胞毒性、细胞因子分泌、脂质过氧化和遗传毒性方面）。
总体而言，本研究表明，本文使用的人体微组织模型是替代传统体外单细胞肝脏模型以及肝脏纳米毒理学进一步发展的极佳候选模型。
