Biomedical Engineering Reference
In-Depth Information
of CNTs induced a dose-dependent increase in LDH release, which is a marker of cell toxicity dur-
ing lung inflammation. CNTs induced a significant increase in lung type I collagen levels in com-
parison with control mice. The authors also reported that a significant fraction of the administered
dose of CNTs (~40%) remained in the lung after 60 days [66,68]. Such reports strongly demand
careful attention to be paid for the application of SWCNTS and MWCNTs.
11.4.1.1 SWCNTs and Pulmonary Toxicity Issues
Alveolar macrophages constitute the first line of immunological defense against invading particles
in the lung. Researchers have conducted a cytotoxicity study of CNTs with macrophages and found
that SWCNTs can induce pulmonary injury in mice. Intratracheal instillations of SWCNTs in the
lungs of rats resulted in the formation of lung granulomas and produced mortality in almost 15%
of rats within 24 h postinstillation due to the enhanced blockage of the large airways. The intratra-
cheal instillation of 0.5 mg of SWCNTs into male imprinting control region (ICR) mice induced the
activation of alveolar macrophages, various chronic inflammatory responses, and severe pulmonary
granuloma formations [69,70]. The SWCNTs have a strong tendency to agglomerate following intra-
tracheal exposures with the propensity to induce interstitial granulomas and pulmonary injuries in
a dose-dependent manner [71]. The macrophage uptake of SWCNTs was observed after the intra-
tracheal instillation of 0.5 mg of SWCNTs, which activated various transcription factors, such as
activator protein 1 (AP-1) and nuclear factor κB (NF-κB). This leads to the induction of protective
and antiapoptotic gene expression, oxidative stress, activation of T cells, recruitment of leukocytes,
and release of proinflammatory cytokines [70].
Investigators also assessed the health risks of CNTs on the human respiratory system by using
cocultures of normal bronchial epithelial cells and normal human fibroblasts. An aqueous solution
of SWCNTs was incubated with the above coculture. The results indicated the increased production
of nitrous oxide and decreased cell viability after exposure to different concentrations of SWCNTs.
The above observations were associated with the inflammatory and cytotoxic effects of SWCNTs,
respectively. The dose administered by inhalation produced greater respiratory toxicities than the
same dose administered by aspiration. The SWCNTs in both a single-dose aspiration study and a
4-day inhalation study caused an early inflammatory response followed by granulomas, fibrosis,
and decreased rates of respiration, as well as the activation of a gene that produces lung cancer [72].
By using adult female C57BL mice, investigators detected two morphologically distinct responses
in the lung as early as 7 days postexposure of SWCNTs delivered by pharyngeal aspiration. CNTs
were clearly associated with an elicited granulomatous inflammatory response, and interfacing bun-
dles of fibrous connective tissue were observed within discrete granulomas.
Reports are also available that confirm the detection of signs of gill irritation and mucus secre-
tion after the exposure of fish to SWCNTs. Visual inspection of the gills and mucus smears on day
4 showed a thin layer of secreted mucus on the surface of gills from fish treated with SWCNTs,
but not the controls. It was found that the exposure to SWCNTs caused respiratory toxicity in trout,
increased mucus secretion, and enlarged mucocytes on the gills; elevated ventilation rates com-
pared with the controls were observed, but no mortalities and gill injuries (swollen tips of lamellae,
enlarged mucocytes, edema) had occurred by the fourth day [73,74]. In the same fashion, serious
toxicity setbacks are also associated with MWCNTs.
11.4.1.2 MWCNTs and Pulmonary Toxicity Issues
With a large size and high phase ratio, MWCNTs caused significant protein exudates and granu-
lomas on the peritoneal side of the diaphragm due to inflammation. The MWCNTs were found to
be present in the lung after 60 days, and both induced inflammatory and fibrotic reactions. After 2
months, collagen-rich granulomas were observed protruding in the bronchial lumen, which was also
associated with alveolitis in the surrounding tissues of the pulmonary tract. This class of CNTs also
stimulated the production of TNF-α in the lungs of treated animals.
In vitro
, ground CNTs initiated
the overproduction of TNF-α by macrophages, and results suggested that CNTs may be potentially
