Hepatic toxicology following single and multiple exposure of engineered nanomaterials utilising a novel primary human 3D liver microtissue model
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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Yn: Particle and fibre toxicology, Cyfrol 11, 20.10.2014, t. 56.
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
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T1 - Hepatic toxicology following single and multiple exposure of engineered nanomaterials utilising a novel primary human 3D liver microtissue model
AU - Kermanizadeh, Ali
AU - Løhr, Mille
AU - Roursgaard, Martin
AU - Messner, Simon
AU - Gunness, Patrina
AU - Kelm, Jens M
AU - Møller, Peter
AU - Stone, Vicki
AU - Loft, Steffen
PY - 2014/10/20
Y1 - 2014/10/20
N2 - BACKGROUND: 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.).METHODS: 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).RESULTS: 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).CONCLUSIONS: 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.
AB - BACKGROUND: 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.).METHODS: 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).RESULTS: 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).CONCLUSIONS: 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.
KW - Cells, Cultured
KW - Chemical and Drug Induced Liver Injury/immunology
KW - Coculture Techniques
KW - Cytokines/agonists
KW - DNA Damage
KW - Hepatocytes/cytology
KW - Humans
KW - Lipid Peroxidation/drug effects
KW - Liver/drug effects
KW - Metal Nanoparticles/chemistry
KW - Microscopy, Electron, Transmission
KW - Nanostructures/chemistry
KW - Nanotubes, Carbon/chemistry
KW - Oxidative Stress/drug effects
KW - Serum Albumin/biosynthesis
KW - Serum Albumin, Human
KW - Silver/chemistry
KW - Stromal Cells/cytology
KW - Titanium/chemistry
KW - Toxicity Tests, Acute/methods
KW - Zinc Oxide/chemistry
U2 - 10.1186/s12989-014-0056-2
DO - 10.1186/s12989-014-0056-2
M3 - Article
C2 - 25326698
VL - 11
SP - 56
JO - Particle and fibre toxicology
JF - Particle and fibre toxicology
SN - 1743-8977
ER -