A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice

Abstract

Large amounts of nanomaterials may reach both the natural and occupational environments. This represents a potential health hazard. People have forecasted that CNTs may lead to the toxicity such as mesothelioma and fibrosis like asbestos. To identify dominant immune responses induced by SWCNTs, we investigated the composition of bronchioalveolar lavage (BAL) cells, the secretion of cytokine and collagen, histopathology, protein expression, and cell phenotypes over time after a single administration of single-walled carbon nanotubes (SWCNT). In our results, the number of total cells and macrophages remained at the up-regulated level until Day 28, neutrophils rapidly increased at Day 1, and lymphocytes increased from Day 7. In the BAL fluid, pro-inflammatory cytokines rapidly increased at Day 1 and remained at an up-regulated level throughout the experimental period. IL-12 and IL-10 rapidly increased at Day 1 after administration and remained at a similar level until Day 28. IFN-γ and IL-4 reached the maximum at Day 1, and IL-5, TGF-β, and collagen reached the maximum at Day 7. IL-13 and IL-17 increased in a time-dependent manner. The distribution of B cells and cytotoxic T cells markedly increased at Days 7 and 14, and fibrotic lesions were histopathologically observed at Days 7 and 14. The expressions of caspase-3, p53, COL1A1, COX-2, iNOS, MMP-9, and MMP-2 were also markedly increased at Days 7 and 14. In addition, the expression of mesothelin, iNOS, MMP-9, and p53 was up-regulated until Day 28. Based on these findings, we suggest that a single intratracheal instillation of SWCNTs may induce early lung fibrosis and subchronic tissue damage.

The role of p53 in lung macrophages following exposure to a panel of manufactured nanomaterials

“…It has been suggested that the p53 protein controls a wide range of cellular processes after MNM exposure which includes oxidative stress, inflammatory response, cell cycle arrest and apoptosis. Indeed, elevated p53 expression (mRNA or protein) and even an activation via phosphorylation of its N-terminal domain have been demonstrated in response to cB, TiO 2 and cNT nanomaterials (Mroz et al 2007(Mroz et al , 2008Park et al 2011;Shi et al 2010). However, to date, p53 has been mainly studied as a marker of apoptosis.…”

“…This p53 induction was associated with cell cycle arrest and apoptosis (Kang et al 2008;Petkovic et al 2011;Wu et al 2010). The involvement of p53 was also implicated in the induction of apoptosis and carcinogenesis following the exposure of cNTs in rodent models (intraperitoneal injection and intratracheal instillation) (Park et al 2011;Poland et al 2008;Takagi et al 2008).…”

Multiwalled carbon nanotubes induce altered morphology and loss of barrier function in human bronchial epithelium at noncytotoxic doses

“…6 Previous studies have demonstrated the ability of MWCNTs to induce pulmonary inflammation, fibrosis, formation of granuloma, and airway injury [7][8][9] when delivered by instillation or inhalation. 10 There is also evidence of oxidative stress 11 and apoptosis 12 in bronchial epithelial airway cells exposed to CNTs in vitro.…”

Nanotoxicology and oxidative stress control: cutting-edge topics in toxicology

“…Overall, there is no convincing evidence of an association (41) Bosetti et al (2010) Transition metal ions induce lipid peroxidation in artificial phospholipid liposomes (42) Repetto et al (2010) The antioxidants, isoquercitrin and melatonin reduce oxidative stress-mediated liver tumour promotion by the benzimidazole anthelmintic, oxfendazole in rats (43) Nishimura et al (2010) Administration of silver nanoparticles to rats caused a dose-dependent accumulation of particles in the lamina propria of the small and large intestine, increased numbers of goblet cells and altered mucus composition (44) Jeong et al (2010) The author critically discusses Hermann J. Muller's well-known Nobel lecture where a linear dose-response for radiation-induced germ cell mutations was presented. In contrast to this concept, Calabrese presents arguments speaking against the linear no-threshold model (45) Calabrese (2011) Zinc oxide nanoparticles induce the release of pro-inflammatory cytokines in mouse and human cell systems (46) Heng et al (2011) A single intratracheal instillation of carbon nanotubes may induce early lung fibrosis (47) Park et al (2011) Indole-3-carbinol and flutamide increased the expression of CYP1A1 and induced liver cell foci in rats (48) Shimamoto et al (2011) Synephrine is added to dietary supplements for weight loss. The hydroxyl group in the p-position favours transporter-mediated uptake into cardiomyocytes.…”