Abstract
The increasing use of carbon nanotubes (CNTs) in several industrial applications raises concerns on their potential toxicity due to factors such as tissue penetrance, small dimensions, and biopersistence. Using an in vivo model for CNT environmental exposure, mimicking CNT exposition at the workplace, we previously found that CNTs rapidly enter and disseminate in the organism, initially accumulating in the lungs and brain and later reaching the liver and kidneys via the bloodstream in CD1 mice. Here, we monitored and traced the accumulation of single-walled CNTs (SWCNTs), administered systemically in mice, in different organs and the subsequent biological responses. Using the novel in vivo model, MITO-Luc bioluminescence reporter mice, we found that SWCNTs induce systemic cell proliferation, indicating a dynamic response of cells of both bone marrow and the immune system. We then examined metabolic (water/food consumption and dejections), functional (serum enzymes), and morphological (organs and tissues) alterations in CD1 mice treated with SWCNTs, using metabolic cages, performing serum analyses, and applying histological, immunohistochemical, and ultrastructural (transmission electron microscopy) methods. We observed a transient accumulation of SWCNTs in the lungs, spleen, and kidneys of CD1 mice exposed to SWCNTs. A dose- and time-dependent accumulation was found in the liver, associated with increases in levels of aspartate aminotransferase, alanine aminotransferase and bilirubinemia, which are metabolic markers associated with liver damage. Our data suggest that hepatic accumulation of SWCNTs associated with liver damage results in an M1 macrophage-driven inflammation.
| Original language | English |
|---|---|
| Pages (from-to) | 4299-4316 |
| Number of pages | 18 |
| Journal | International Journal of Nanomedicine |
| Volume | 11 |
| DOIs | |
| Publication status | Published - Sep 1 2016 |
Fingerprint
Keywords
- Hepatic function
- Inflammation
- Kupffer cells
- Metabolism
- Mouse models
- Nanotoxicity
- Single-walled carbon nanotubes
ASJC Scopus subject areas
- Biophysics
- Bioengineering
- Biomaterials
- Organic Chemistry
- Drug Discovery
Cite this
Systemic distribution of single-walled carbon nanotubes in a novel model : Alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo. / Principi, Elisa; Girardello, Rossana; Bruno, Antonino; Manni, Isabella; Gini, Elisabetta; Pagani, Arianna; Grimaldi, A.; Ivaldi, Federico; Congiu, T.; De Stefano, Daniela; Piaggio, Giulia; De Eguileor, Magda; Noonan, Douglas M; Albini, Adriana.
In: International Journal of Nanomedicine, Vol. 11, 01.09.2016, p. 4299-4316.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Systemic distribution of single-walled carbon nanotubes in a novel model
T2 - Alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo
AU - Principi, Elisa
AU - Girardello, Rossana
AU - Bruno, Antonino
AU - Manni, Isabella
AU - Gini, Elisabetta
AU - Pagani, Arianna
AU - Grimaldi, A.
AU - Ivaldi, Federico
AU - Congiu, T.
AU - De Stefano, Daniela
AU - Piaggio, Giulia
AU - De Eguileor, Magda
AU - Noonan, Douglas M
AU - Albini, Adriana
PY - 2016/9/1
Y1 - 2016/9/1
N2 - The increasing use of carbon nanotubes (CNTs) in several industrial applications raises concerns on their potential toxicity due to factors such as tissue penetrance, small dimensions, and biopersistence. Using an in vivo model for CNT environmental exposure, mimicking CNT exposition at the workplace, we previously found that CNTs rapidly enter and disseminate in the organism, initially accumulating in the lungs and brain and later reaching the liver and kidneys via the bloodstream in CD1 mice. Here, we monitored and traced the accumulation of single-walled CNTs (SWCNTs), administered systemically in mice, in different organs and the subsequent biological responses. Using the novel in vivo model, MITO-Luc bioluminescence reporter mice, we found that SWCNTs induce systemic cell proliferation, indicating a dynamic response of cells of both bone marrow and the immune system. We then examined metabolic (water/food consumption and dejections), functional (serum enzymes), and morphological (organs and tissues) alterations in CD1 mice treated with SWCNTs, using metabolic cages, performing serum analyses, and applying histological, immunohistochemical, and ultrastructural (transmission electron microscopy) methods. We observed a transient accumulation of SWCNTs in the lungs, spleen, and kidneys of CD1 mice exposed to SWCNTs. A dose- and time-dependent accumulation was found in the liver, associated with increases in levels of aspartate aminotransferase, alanine aminotransferase and bilirubinemia, which are metabolic markers associated with liver damage. Our data suggest that hepatic accumulation of SWCNTs associated with liver damage results in an M1 macrophage-driven inflammation.
AB - The increasing use of carbon nanotubes (CNTs) in several industrial applications raises concerns on their potential toxicity due to factors such as tissue penetrance, small dimensions, and biopersistence. Using an in vivo model for CNT environmental exposure, mimicking CNT exposition at the workplace, we previously found that CNTs rapidly enter and disseminate in the organism, initially accumulating in the lungs and brain and later reaching the liver and kidneys via the bloodstream in CD1 mice. Here, we monitored and traced the accumulation of single-walled CNTs (SWCNTs), administered systemically in mice, in different organs and the subsequent biological responses. Using the novel in vivo model, MITO-Luc bioluminescence reporter mice, we found that SWCNTs induce systemic cell proliferation, indicating a dynamic response of cells of both bone marrow and the immune system. We then examined metabolic (water/food consumption and dejections), functional (serum enzymes), and morphological (organs and tissues) alterations in CD1 mice treated with SWCNTs, using metabolic cages, performing serum analyses, and applying histological, immunohistochemical, and ultrastructural (transmission electron microscopy) methods. We observed a transient accumulation of SWCNTs in the lungs, spleen, and kidneys of CD1 mice exposed to SWCNTs. A dose- and time-dependent accumulation was found in the liver, associated with increases in levels of aspartate aminotransferase, alanine aminotransferase and bilirubinemia, which are metabolic markers associated with liver damage. Our data suggest that hepatic accumulation of SWCNTs associated with liver damage results in an M1 macrophage-driven inflammation.
KW - Hepatic function
KW - Inflammation
KW - Kupffer cells
KW - Metabolism
KW - Mouse models
KW - Nanotoxicity
KW - Single-walled carbon nanotubes
UR - http://www.scopus.com/inward/record.url?scp=84985946860&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84985946860&partnerID=8YFLogxK
U2 - 10.2147/IJN.S109950
DO - 10.2147/IJN.S109950
M3 - Article
VL - 11
SP - 4299
EP - 4316
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
SN - 1176-9114
ER -