Mouse pulmonary dose- and time course-responses induced by exposure to nitrogen-doped multi-walled carbon nanotubes

Autor:	Lori A. Battelli, Bean T. Chen, Marlene S. Orandle, Peng Zheng, Michael G. Wolfarth, Raymond F. Hamilton, Mauricio Terrones, Shuji Tsuruoka, Dale W. Porter, Michael E. Andrew, Vince Castranova, Nianqiang Wu, Andrij Holian
Rok vydání:	2020
Předmět:	Male Time Factors Inflammasomes Nitrogen Surface Properties THP-1 Cells Health Toxicology and Mutagenesis Carbon nanotube 010501 environmental sciences Toxicology 01 natural sciences Article law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law In vivo Lactate dehydrogenase Macrophages Alveolar Animals Humans Particle Size High-resolution transmission electron microscopy Lung 0105 earth and related environmental sciences Inhalation Exposure Dose-Response Relationship Drug Nanotubes Carbon Pneumonia In vitro Mice Inbred C57BL 030228 respiratory system chemistry Transmission electron microscopy Alveolar macrophage Phorbol Biophysics Cytokines Bronchoalveolar Lavage Fluid
Zdroj:	Inhal Toxicol
ISSN:	1091-7691 0895-8378
DOI:	10.1080/08958378.2020.1723746
Popis:	Objective: In this study, we compared in vitro and in vivo bioactivity of nitrogen-doped multi-walled carbon nanotubes (NDMWCNT) to MWCNT to test the hypothesis that nitrogen doping would alter bioactivity.Materials and Methods: High-resolution transmission electron microscopy (TEM) confirmed the multilayer structure of MWCNT with an average layer distance of 0.36 nm, which was not altered by nitrogen doping: the nanomaterials had similar widths and lengths. In vitro studies with THP-1 cells and alveolar macrophages from C57BL/6 mice demonstrated that NDMWCNT were less cytotoxic and stimulated less IL-1β release compared to MWCNT. For in vivo studies, male C57BL/6J mice received a single dose of dispersion medium (DM), 2.5, 10 or 40 µg/mouse of NDMWCNT, or 40 µg/mouse of MWCNT by oropharyngeal aspiration. Animals were euthanized between 1 and 7 days post-exposure for whole lung lavage (WLL) studies.Results and Discussion: NDMWCNT caused time- and dose-dependent pulmonary inflammation. However, it was less than that caused by MWCNT. Activation of the NLRP3 inflammasome was assessed in particle-exposed mice by determining cytokine production in WLL fluid at 1 day post-exposure. Compared to DM-exposed mice, IL-1β and IL-18 were significantly increased in MWCNT- and NDMWCNT-exposed mice, but the increase caused by NDMWCNT was less than MWCNT. At 56 days post-exposure, histopathology determined lung fibrosis in MWCNT-exposed mice was greater than NDMWCNT-exposed mice.Conclusions: These data indicate nitrogen doping of MWCNT decreases their bioactivity, as reflected with lower in vitro and in vivo toxicity inflammation and lung disease. The lower activation of the NLRP3 inflammasome may be responsible. Abbreviations: NDMWCNT: nitrogen-doped multi-walled carbon nanotubes; MWCNT: multi-walled carbon nanotubes; TEM: transmission electron microscopy; HRTEM: high resolution transmission electron microscopy; IL-1s: interleukin-1s; DM: dispersion medium; WLL: whole lung lavage; IL-18: interleukin-18; GSD: geometric standard deviation; XPS: X-ray photoelectron spectroscopy; SEM: standard error of the mean; PMA: phorbol 12-myristate 13-acetate; LPS: lipopolysacharride; LDH: lactate dehydrogenase; AM: alveolar macrophage; PMN: polymorphonuclear leukocyte.
Databáze:	OpenAIRE
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