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Sci Total Environ. 2018 Dec 10;644:907-915. doi: 10.1016/j.scitotenv.2018.06.301. Epub 2018 Jul 11.

Nanoparticles in the lungs of old mice: Pulmonary inflammation and oxidative stress without procoagulant effects.

Author information

1
Department of Public Health and Primary Care, Occupational and Environmental Toxicology, KU Leuven, Leuven, Belgium.
2
Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
3
Department of Public Health and Primary Care, Laboratory for Occupational and Environmental Hygiene, KU Leuven, Leuven, Belgium.
4
Department of Public Health and Primary Care, Occupational and Environmental Toxicology, KU Leuven, Leuven, Belgium; Department of Public Health and Primary Care, Laboratory for Occupational and Environmental Hygiene, KU Leuven, Leuven, Belgium.
5
Department of Public Health and Primary Care, Occupational and Environmental Toxicology, KU Leuven, Leuven, Belgium. Electronic address: peter.hoet@kuleuven.be.

Abstract

Pulmonary exposure to nanoparticles (NPs) has been shown to induce pulmonary as well as cardiovascular toxicity. These effects might be enhanced in elderly subjects as a result of a compromised immunity and/or declined organ functions. To study the adverse in vivo effects of NPs in a model for the elderly, we exposed 18-month-old C75Bl/6 mice to multi-walled carbon nanotubes (MWCNTs) or ZnO NPs by intratracheal instillation once a week during 5 consecutive weeks. Pulmonary and hemostatic toxicity was determined 24 h (T1) and 8 weeks (T2) after the last administration. Both NP types significantly increased the pulmonary macrophages at both time points. The MWCNTs and ZnO NPs also induced a pulmonary influx of neutrophils, which was even larger at T2 compared to T1. All NPs induced only a modest increase of pulmonary IL-1β, IL-6 and KC levels. Both types of NPs also increased blood neutrophils. Red blood cells were not significantly affected. Both NPs significantly increased coagulation factor VIII levels at both time points. Histological analysis revealed the presence of MWCNTs in the alveolar macrophages up to 8 weeks after the last administration and the ZnO NPs induced a pronounced alveolar inflammation. In these 18-month-old mice, NPs caused pulmonary inflammation (without evidence of oxidative stress) accompanied by large increases in coagulation factor VIII up to 8 weeks after the last NP exposure. The persistence of the MWCNTs in the lungs resulted in translocation from the lungs to the left heart and the ZnO NPs induced a fibrosis-like pathology.

KEYWORDS:

Fibrosis; Hemostasis parameters; Old mice; Oxidative stress; Pulmonary inflammation

PMID:
30743888
DOI:
10.1016/j.scitotenv.2018.06.301
[Indexed for MEDLINE]

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