Assessment of temporal dose-toxicity relationship of fumed silica nanoparticle in human lung A549 cells by conventional cytotoxicity and 1H-NMR-based extracellular metabonomic assays.

Irfan, Adeel; Cauchi, Michael; Edmands, William; Gooderham, Nigel J.; Njuguna, James; Zhu, Huijun

Abstract

As nanoparticles could form aggregates in biological systems, the dynamics of their dispersity drives the temporal effect of nanoparticles in vitro. To test this hypothesis, the fumed silica nanoparticles (SiNPs) that have primary sizes of 7-14 nm and form aggregates in culture medium were selected for toxicity study in human lung A549 cells. The dispersity of SiNPs was analyzed by dynamic light scattering and transmission of electron microscopy. Cytotoxicity assays including mitochondrial activity, intracellular level of reactive oxygen species (ROS), and membrane damage together with the 1H-NMR-based extracellular metabonomic assay were conducted to determine the temporal dose-effect relationship of SiNPs. In cell culture medium, SiNPs dispersed well initially at 25-100 μg/ml; however, they sedimented rapidly in a concentration-dependent manner. SiNPs caused a dose-dependent increase of intracellular ROS and cell membrane damage at 4 h and a loss of cell viability after 48 h. SiNPs also induced an elevation of extracellular glucose, lactate, phenylalanine, histidine, and tyrosine levels in a time- and concentration-dependent manner. The dose-effect patterns at 4 h were different from that at 12 and 24 h as assessed by both cytotoxicity and metabonomic assays. Both fitted better with polynomial regression than linear regression, implying multimode action of SiNPs at different concentrations. The early NP-cell interaction and the late sedimentation could be attributable to the temporal effects of SiNPs. The extracellular 1H-NMR-based metabonomics demonstrated a potential as a robust nondestructive tool for monitoring the temporal effect of NPs that tend to aggregate in nature.

Citation

IRFAN, A., CAUCHI, M., EDMANDS, W., GOODERHAM, N. J., NJUGUNA, J. and ZHU, H. 2014. Assessment of temporal dose-toxicity relationship of fumed silica nanoparticle in human lung A549 cells by conventional cytotoxicity and 1H-NMR-based extracellular metabonomic assays. Toxicological sciences [online], 138 (2), pages 354-364. Available from: https://doi.org/10.1093/toxsci/kfu009

• Journal Article Type: Article
• Acceptance Date: Jan 9, 2014
• Online Publication Date: Jan 21, 2014
• Publication Date: Apr 30, 2014
• Deposit Date: Jan 22, 2015
• Publicly Available Date: Jan 22, 2015
• Journal: Toxicological sciences
• Print ISSN: 1096-6080
• Electronic ISSN: 1096-0929
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 138
• Issue: 2
• Pages: 354-364
• DOI: https://doi.org/10.1093/toxsci/kfu009
• Keywords: Fumed silica nanoparticles; A549 cells; HNMR metabonomics; Dose effect relationship
• Public URL: http://hdl.handle.net/10059/1130
• Contract Date: Jan 22, 2015