Translocation of Intratracheally Instilled Multiwall Carbon Nanotubes to Lung-Associated Lymph Nodes in Rats

Aiso, Shigetoshi; Kubota, Hisayo; Umeda, Yumi; Kasai, Tatsuya; Takaya, Mitsutoshi; Yamazaki, Kazunori; Nagano, Kasuke; Sakai, Toshio; Koda, Shigeki; Fukushima, Shoji

doi:10.2486/indhealth.ms1213

Cited by 28 publications

(23 citation statements)

References 13 publications

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“…Translocation of MWCNT from the lung to the tracheobronchial lymph node has previously been demonstrated in rats (Aiso et al 2011). Increased paracortical cellularity has also been previously noted in the lymph nodes of rats inhaling MWCNT (Pauluhn 2010).…”

Section: Discussionmentioning

confidence: 87%

Acute pulmonary dose–responses to inhaled multi-walled carbon nanotubes

et al. 2012

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This study investigated the in vivo pulmonary toxicity of inhaled multi-walled carbon nanotubes (MWCNT). Mice-inhaled aerosolized MWCNT (10 mg/m³, 5 h/day) for 2, 4, 8 or 12 days. MWCNT lung burden was linearly related to exposure duration. MWCNT-induced pulmonary inflammation was assessed by determining whole lung lavage (WLL) polymorphonuclear leukocytes (PMN). Lung cytotoxicity was assessed by WLL fluid LDH activities. WLL fluid albumin concentrations were determined as a marker of alveolar air-blood barrier integrity. These parameters significantly increased in MWCNT-exposed mice versus controls and were dose-dependent. Histopathologic alterations identified in the lung included (1) bronciolocentric inflammation, (2) bronchiolar epithelial hyperplasia and hypertrophy, (3) fibrosis, (4) vascular changes and (5) rare pleural penetration. MWCNT translocated to the lymph node where the deep paracortex was expanded after 8 or 12 days. Acute inhalation of MWCNT induced dose-dependent pulmonary inflammation and damage with rapid development of pulmonary fibrosis, and also demonstrated that MWCNT can reach the pleura after inhalation exposure.

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Section: Discussionmentioning

confidence: 87%

Acute pulmonary dose–responses to inhaled multi-walled carbon nanotubes

et al. 2012

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“…The authors noted that the deposition of the NMs was greater in the posterior mediastinal lymph node than in the parathymic lymph node. However, it should be noted that the presence of MWCNTs was evaluated by microscopic observations in haematoxylin and eosin-stained tissues (Aiso et al 2011). …”

Section: Intratracheal Instillationmentioning

confidence: 99%

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

Kermanizadeh

Balharry

Wallin

et al. 2015

Critical Reviews in Toxicology

139

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Engineered nanomaterials (NMs) offer great technological advantages but their risks to human health are still not fully understood. An increasing body of evidence suggests that some NMs are capable of distributing from the site of exposure to a number of secondary organs. The research into the toxicity posed by the NMs in these secondary organs is expanding due to the realisation that some materials may reach and accumulate in these target sites. The translocation to secondary organs includes, but is not limited to, the hepatic, central nervous, cardiovascular and renal systems. Current data indicates that pulmonary exposure is associated with low (inhalation route-0.00001-1% of total applied dose-24 h) translocation of virtually insoluble NMs such as iridium, carbon black, gold and polystyrene, while slightly higher translocation has been observed for NMs with either slow (e.g., silver, cerium dioxide and quantum dots) or fast (e.g., zinc oxide) solubility. The translocation of NMs following intratracheal, intranasal and pharyngeal aspiration is higher (up to 10% of administered dose), however the relevance of these routes for risk assessment is questionable. Uptake of the materials from the gastrointestinal tract seems to follow the same pattern as inhalation translocation, whereas the dermal uptake of NMs is generally reported to be low. The toxicological effects in secondary organs include oxidative stress, inflammation, cytotoxicity and dysfunction of cellular and physiological processes. For toxicological and risk evaluation, further information on the toxicokinetics and persistence of NMs is crucial. The overall aim of this review is to outline the data currently available in the literature on the biokinetics, accumulation, toxicity and eventual fate of NMs in order to assess the potential risks posed by NMs to secondary organs.

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“…Indeed, in vivo studies reported that MWCNT induced inflammation, granuloma formation, and persistent interstitial fibrosis (Porter et al, 2010; Takagi et al, 2008). Following intraperitonael (IP) administration, Aiso et al (2010; 2011) demonstrated that MWCNT were detected in the lung 60 days post-exposure. In vitro studies showed that exposure of lung and skin cells to MWCNT induced cytotoxic effects, oxidative stress, and genotoxic effects (Asakura et al, 2010; Patlolla et al, 2010; Wang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Cell Permeability, Migration, and Reactive Oxygen Species Induced by Multiwalled Carbon Nanotubes in Human Microvascular Endothelial Cells

Pacurari

Qian

et al. 2011

Journal of Toxicology and Environmental Health, Part A

103

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Multi-walled carbon nanotubes (MWCNT) have elicited great interest in biomedical applications due to their extraordinary physical, chemical, and optical properties. Intravenous administration of MWCNT-based medical imaging agents and drugs in animal models was utilized. However, the potential harmful health effects of MWCNT administration in humans have not yet been elucidated. Furthermore, to date, there are no apparent reports regarding the precise mechanisms of translocation of MWCNT into target tissues and organs from blood circulation. This study demonstrates that exposure to MWCNT leads to an increase in cell permeability in human microvascular endothelial cells (HMVEC). The results obtained from this study also showed that the MWCNT-induced rise in endothelial permeability is mediated by reactive oxygen species (ROS) production and actin filament remodeling. In addition, it was found that MWCNT promoted cell migration in HMVEC. Mechanistically, MWCNT exposure elevated the levels of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule 1 (ICAM-1) in HMVEC. Taken together, these results provide new insights into the bioreactivity of MWCNT, which may have implications in the biomedical application of MWCNT in vascular targeting, imaging, and drug delivery. The results generated from this study also elucidate the potential adverse effects of MWCNT exposure on humans at the cellular level.

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Translocation of Intratracheally Instilled Multiwall Carbon Nanotubes to Lung-Associated Lymph Nodes in Rats

Cited by 28 publications

References 13 publications

Acute pulmonary dose–responses to inhaled multi-walled carbon nanotubes

Acute pulmonary dose–responses to inhaled multi-walled carbon nanotubes

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

Cell Permeability, Migration, and Reactive Oxygen Species Induced by Multiwalled Carbon Nanotubes in Human Microvascular Endothelial Cells

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