Systemic distribution of single-walled carbon nanotubes in a novel model: Alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo

Elisa Principi, Rossana Girardello, Antonino Bruno, Isabella Manni, Elisabetta Gini, Arianna Pagani, A. Grimaldi, Federico Ivaldi, T. Congiu, Daniela De Stefano, Giulia Piaggio, Magda De Eguileor, Douglas M Noonan, Adriana Albini

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)4299-4316
Number of pages18
JournalInternational Journal of Nanomedicine
Volume11
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Carbon Nanotubes
Single-walled carbon nanotubes (SWCN)
Liver
Carbon nanotubes
Inflammation
Tissue
Bioluminescence
Macrophages
Immune system
Cell proliferation
Kidney
Aspartate Aminotransferases
Lung
Alanine Transaminase
Hyperbilirubinemia
Penetrance
Industrial applications
Dynamic response
Environmental Exposure
Toxicity

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 journalArticle

Principi, E, Girardello, R, Bruno, A, Manni, I, Gini, E, Pagani, A, Grimaldi, A, Ivaldi, F, Congiu, T, De Stefano, D, Piaggio, G, De Eguileor, M, Noonan, DM & Albini, A 2016, 'Systemic distribution of single-walled carbon nanotubes in a novel model: Alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo', International Journal of Nanomedicine, vol. 11, pp. 4299-4316. https://doi.org/10.2147/IJN.S109950
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. / Systemic distribution of single-walled carbon nanotubes in a novel model : Alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo. In: International Journal of Nanomedicine. 2016 ; Vol. 11. pp. 4299-4316.
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