Toxicological effects of nanoparticle deposition in the liver

Justyna Modrzynska

Research output: Book/ReportPh.D. thesis

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A number of studies have demonstrated that pulmonary exposure to nanoparticles (NPs) by inhalation or intratracheal instillation leads to size-dependent accumulation of particles and causes adverse pulmonary effects including, among others, inflammation, induction of acute phase response and histopathological alterations of the lung tissue. Upon deposition in the respiratory tract particles appear to translocate readily across the alveolar epithelium, through interstitium and further into systemic circulation getting access to the extrapulmonary sites and reaching various distant organs. The degree of translocation strongly depends on particles size, chemical composition, solubility, shape, surface properties etc. A portion of lung-deposited particles could also be transported up into the pharynx by the mucociliary escalator and when swallowed, cause secondary exposure via gastrointestinal tract(GIT). Liver, among other secondary organs, seems to be the major tissue for sequestration of extrapulmonary-translocated NPs. When particles reach the liver, they accumulate in the Kupffer cells, residence liver macrophages, from where their clearance is protracted. It has been shown that particles were still present in the liver 6 months after exposure. Prolonged hepatic accumulation of NPsraises questions about the possible acute and long-term toxicological consequences.
Deposition of NPsin the liver makes it very susceptible to many diseases and causesdisturbances in its normal functioning. Our research group has previously demonstrated that inhalation and intratracheal instillation of CB Printex 90 and TiO2NPs induced genotoxicity in terms of increased DNA strand break levels and increased levels of oxidative DNA damage in the liver tissue. Moreover, recent epidemiological studies indicated association between exposure to particulate air pollutions and development of liver cancer.
This PhD aimed at investigating toxicological effects of NP accumulation in the liver. We have decided to focus primarily on NP-elicited genotoxicity, inflammation, acute phase response as well as evaluating several other systemic endpoints including histopathologyof lung and liver tissue, general liver biochemistry and haematology. Extrapulmonary translocation and liver deposition were also assessed in the study. Close attention was given to the nature of NP-induced genotoxicity observed in the liver tissue – whether it is caused by the presence of translocated particles or by indirect effects of inflammation and acute phase response in the lungs that could trigger production of secondary messengers and, in turn, induce secondary genotoxicity in the liver tissue. Moreover, potential contribution from the secondary oral exposure could also result in the observed genotoxic effect.
To achieve the aims 324 young adult C57BL/6 female mice were exposed by single intratracheal instillation (IT), intravenous injection (IV)and oral gavage (PO) to 162 μg/mouse of titanium dioxide (TiO2), cerium oxide (CeO2) or carbon black (CB) NPs and terminated 1, 28 and 180 days post-exposure.
Original languageEnglish
Place of PublicationKgs. Lyngby, Denmark
PublisherTechnical University of Denmark
Number of pages189
ISBN (Electronic)978-87-93565-05-0
Publication statusPublished - 2018


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