Aspect ratio plays a role in the hazard potential of CeO2 nanoparticles in mouse lung and zebrafish gastrointestinal tract.
We have previously demonstrated that there is a relationship between the aspect ratio (AR) of CeO2 nanoparticles and in vitro hazard potential. CeO2 nanorods with AR ≥ 22 induced lysosomal damage and progressive effects on IL-1β production and cytotoxicity in the human myeloid cell line, THP-1. In order to determine whether this toxicological paradigm for long aspect ratio (LAR) CeO2 is also relevant in vivo, we performed comparative studies in the mouse lung and gastrointestinal tract (GIT) of zebrafish larvae. Although oropharyngeal aspiration could induce acute lung inflammation for CeO2 nanospheres and nanorods, only the nanorods with the highest AR (C5) induced significant IL-1β and TGF-β1 production in the bronchoalveolar lavage fluid at 21 days but did not induce pulmonary fibrosis. However, after a longer duration (44 days) exposure to 4 mg/kg of the C5 nanorods, more collagen production was seen with CeO2 nanorods vs nanospheres after correcting for Ce lung burden. Using an oral-exposure model in zebrafish larvae, we demonstrated that C5 nanorods also induced significant growth inhibition, a decrease in body weight, and delayed vertebral calcification. In contrast, CeO2 nanospheres and shorter nanorods had no effect. Histological and transmission electron microscopy analyses showed that the key injury mechanism of C5 was in the epithelial lining of the GIT, which demonstrated blunted microvilli and compromised digestive function. All considered, these data demonstrate that, similar to cellular studies, LAR CeO2 nanorods exhibit more toxicity in the lung and GIT, which could be relevant to inhalation and environmental hazard potential.
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, ‡Department of Molecular, Cell and Developmental Biology, §Division of NanoMedicine, Department of Medicine, ∥Department of Materials Science and Engineering, ⊥Brain Research Institute, and ⊗Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
Sijie
S
Lin
Xiang
X
Wang
Zhaoxia
Z
Ji
Chong Hyun
CH
Chang
Yuan
Y
Dong
Huan
H
Meng
Yu-Pei
YP
Liao
Meiying
M
Wang
Tze-Bin
TB
Song
Sirus
S
Kohan
Tian
T
Xia
Jeffrey I
JI
Zink
Shuo
S
Lin
André E
AE
Nel
D000818:Animals; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D002563:Cerium / Q000737:chemistry*; D005355:Fibrosis / Q000473:pathology; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006801:Humans; D007249:Inflammation; D007814:Larva / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D054118:Nanospheres / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D037742:Nanotubes, Carbon / Q000737:chemistry; D016016:Proportional Hazards Models; D053120:Respiratory Aspiration; D015027:Zebrafish
D037742:Nanotubes, Carbon; D002563:Cerium; C030583:ceric oxide