Toxicity and clearance of intratracheally administered multiwalled carbon nanotubes from murine lung.

Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Journal of Toxicology and Environmental Health Part A (Impact Factor: 1.73). 01/2010; 73(21-22):1530-43. DOI: 10.1080/15287394.2010.511578
Source: PubMed

ABSTRACT Carbon nanotubes (CNT) are known to have widespread industrial applications; however, several reports indicated that these compounds may be associated with adverse effects in humans. In this study, multiwalled carbon nanotubes were administered to murine lungs intratracheally to determine whether acute and chronic pulmonary toxicity occurred. In particular, pristine multiwalled carbon nanotubes (PMWCNT) and acid-treated multiwalled carbon nanotubes (TMWCNT) were used in this study. In broncheoalveolar lavage fluid (BALF) cell analysis, PMWCNT induced more severe acute inflammatory cell recruitment than TMWCNT. Histopathologically, both PMWCNT and TMWCNT induced multifocal inflammatory granulomas in a dose-dependent manner. The observed granulomas were reversible, with TMWCNT-induced granulomas diminishing faster than PMWCNT-induced granulomas. Although the area of granuloma reduced with time, hyperplasia and dysplastic characteristics such as mitotic figures, anisokaryosis, and anisocytosis were still observed. These findings demonstrate that MWCNT induces granulomatous inflammation, and the duration and pattern of inflammation seem to vary depending upon the types of MWCNT to which mice are exposed. Therefore, toxicity studies on various types of CNT are needed as the responsiveness to these compounds differs.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Magnetic nanoparticles (MNPs) represent a subclass within the overall category of nanomaterials and are widely used in many applications, particularly in the biomedical sciences such as targeted delivery of drugs or genes, in magnetic resonance imaging, and in hyperthermia (treating tumors with heat). Although the potential benefits of MNPs are considerable, there is a distinct need to identify any potential toxicity associated with these MNPs. The potential of MNPs in drug delivery stems from the intrinsic properties of the magnetic core combined with their drug loading capability and the biomedical properties of MNPs generated by different surface coatings. These surface modifications alter the particokinetics and toxicity of MNPs by changing protein-MNP or cell-MNP interactions. This review contains current advances in MNPs for drug delivery and their possible organ toxicities associated with disturbance in body iron homeostasis. The importance of protein-MNP interactions and various safety considerations relating to MNP exposure are also addressed.
    Archives of Toxicology 11/2011; 86(5):685-700. · 5.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Rapid increase in multi-walled carbon nanotube (MWCNT) production for their industrial and biomedical applications has led to concerns over the effects of MWCNTs on human health and the environment. Both animal and in vitro studies have provided important findings about MWCNT-induced effects on the lung cells or tissues. In vitro studies have provided a considerable amount of fundamental information on MWCNT-induced effects on the specific lung cells. However, the cell culture systems used in those studies were limited by the absence of dynamic nature of lung tissues. We hypothesized that MWCNT-induced cellular responses such as proliferation, inflammation, and oxidative stress under dynamic cell growth environment may differ from those under static cell growth environment. RESULTS: In this study, we used a dynamic cell growth condition to mimic mechanically dynamic environment of the lung and characterized interleukin 8 (IL-8), reactive oxygen species (ROS), glutathione (GSH), and cell proliferation for three days following exposure of MWCNTs at different concentrations (5, 10, and 20 mug/ml) to A549 cell monolayer under both static and dynamic cell growth conditions. Our results demonstrated the distinct differences in the levels of inflammatory response and oxidative stress between static and dynamic cell growth conditions. CONCLUSIONS: In conclusion, the dynamic cell growth system used in this study provided important changes in cellular responses that were not found in the static cell growth system and were similar to animal studies. The dynamic cell growth system can be considered as a viable alternative to in vivo test system in combination with existing in vitro static cell growth systems to evaluate the effect of MWCNTs on cellular responses in the respiratory system.
    Journal of Biological Engineering 11/2012; 6(1):22.
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing concern about the toxicity of inhaled multi-walled carbon nanotubes (MWCNTs). Pulmonary macrophages represent the primary cell type involved in the clearance of inhaled particulate materials, and induction of apoptosis in these cells has been considered to contribute to the development of lung fibrosis. We have investigated the apoptotic, inflammogenic, and fibrogenic potential of two types of MWCNTs, characterised by a contrasting average tube length and entanglement/agglomeration. Both nanotube types triggered H2O2 formation by RAW 264.7 macrophages, but in vitro toxicity was exclusively seen with the longer MWCNT. Both types of nanotubes caused granuloma in the mouse lungs. However, the long MWCNT induced a more pronounced pro-fibrotic (mRNA expression of matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1) and inflammatory (serum level of monocyte chemotactic protein-1) response. Masson trichrome staining also revealed epithelial cell hyperplasia for this type of MWCNT. Enhanced apoptosis was detected by cleaved caspase 3 immunohistochemistry in lungs of mice treated with the long and rigid MWCNT and, to a lesser extent, with the shorter, highly agglomerated MWCNT. However, staining was merely localised to granulomatous foci, and neither of the MWCNTs induced apoptosis in vitro, evaluated by caspase 3/7 activity in RAW 264.7 cells. In addition, our study reveals that the inflammatory and pro-fibrotic effects of MWCNTs in the mouse lung can vary considerably depending on their composition. The in vitro analysis of macrophage apoptosis appears to be a poor predictor of their pulmonary hazard.
    Archives of Toxicology 03/2014; · 5.22 Impact Factor