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,1,* Rossana Girardello,2,* Antonino Bruno,1,* Isabella Manni,3 Elisabetta Gini,2 Arianna Pagani,1 Annalisa Grimaldi,2 Federico Ivaldi,4 Terenzio Congiu,5 Daniela De Stefano,1 Giulia Piaggio,3 Magda de Eguileor,2 Douglas M Noonan,1,2 Adriana Albini1 1Vascular Biology and Angiogenesis,...
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Dove Medical Press
2016
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oai:doaj.org-article:56b53f4a2c4d4336a66ff75b3036196a2021-12-02T02:32:06ZSystemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo1178-2013https://doaj.org/article/56b53f4a2c4d4336a66ff75b3036196a2016-09-01T00:00:00Zhttps://www.dovepress.com/systemic-distribution-of-single-walled-carbon-nanotubes-in-a-novel-mod-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Elisa Principi,1,* Rossana Girardello,2,* Antonino Bruno,1,* Isabella Manni,3 Elisabetta Gini,2 Arianna Pagani,1 Annalisa Grimaldi,2 Federico Ivaldi,4 Terenzio Congiu,5 Daniela De Stefano,1 Giulia Piaggio,3 Magda de Eguileor,2 Douglas M Noonan,1,2 Adriana Albini1 1Vascular Biology and Angiogenesis, Scientific and Technology Pole, IRCCS MultiMedica, Milano, 2Department of Biotechnology and Life Sciences, University of Insubria, Varese, 3Department of Research, Advanced Diagnosis and Innovation, Regina Elena National Cancer Institute, Rome, 4Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, 5Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy *These authors contributed equally to this work 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. Keywords: single-walled carbon nanotubes, nanotoxicity, metabolism, hepatic function, inflammation, Kupffer cells, mouse modelsPrincipi EGirardello RBruno AManni IGini EPagani AGrimaldi AIvaldi FCongiu TDe Stefano DPiaggio Gde Eguileor MNoonan DMAlbini ADove Medical Pressarticlesingle-walled carbon nanotubesnanotoxicitymetabolic functionliverinflammationmacrophagesmouse models.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4299-4316 (2016) |
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single-walled carbon nanotubes nanotoxicity metabolic function liver inflammation macrophages mouse models. Medicine (General) R5-920 |
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single-walled carbon nanotubes nanotoxicity metabolic function liver inflammation macrophages mouse models. Medicine (General) R5-920 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 Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo |
| description |
Elisa Principi,1,* Rossana Girardello,2,* Antonino Bruno,1,* Isabella Manni,3 Elisabetta Gini,2 Arianna Pagani,1 Annalisa Grimaldi,2 Federico Ivaldi,4 Terenzio Congiu,5 Daniela De Stefano,1 Giulia Piaggio,3 Magda de Eguileor,2 Douglas M Noonan,1,2 Adriana Albini1 1Vascular Biology and Angiogenesis, Scientific and Technology Pole, IRCCS MultiMedica, Milano, 2Department of Biotechnology and Life Sciences, University of Insubria, Varese, 3Department of Research, Advanced Diagnosis and Innovation, Regina Elena National Cancer Institute, Rome, 4Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, 5Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy *These authors contributed equally to this work 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. Keywords: single-walled carbon nanotubes, nanotoxicity, metabolism, hepatic function, inflammation, Kupffer cells, mouse models |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Principi E |
| title |
Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo |
| title_short |
Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo |
| title_full |
Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo |
| title_fullStr |
Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo |
| title_full_unstemmed |
Systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo |
| title_sort |
systemic distribution of single-walled carbon nanotubes in a novel model: alteration of biochemical parameters, metabolic functions, liver accumulation, and inflammation in vivo |
| publisher |
Dove Medical Press |
| publishDate |
2016 |
| url |
https://doaj.org/article/56b53f4a2c4d4336a66ff75b3036196a |
| work_keys_str_mv |
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