Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study

Abstract

Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration and lactate dehydrogenase (LDH) activity and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 month, 6 months, and 1 year post-exposure. As MWCNT are often structurally compared to asbestos, a 120 μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all 3 post-exposure times. Asbestos exposure elevated LDH activity at all 3 post-exposure times and PMN infiltration at 1- and 6 months post-exposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 year post-exposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, we determined up- and down-regulated gene expression in lung tissue at 1 year post-exposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological changes similar to crocidolite asbestos, but may reach these endpoints by different mechanisms.

Conventional and novel “omics”‐based approaches to the study of carbon nanotubes pulmonary toxicity

“…In line with the present findings, MWCNT exposure tended to impact on genes and pathways involved in immune responses (Snyder-Talkington et al, 2016a). Conversely, the annotated pathways identified in this exercise, when considered in isolation from each other, may not allow differentiating Mitsui-7 exposure from that of other inhaled toxicants.…”

“…DOI 10.1002/em evidenced by the dose-dependent elevation in lactate dehydrogenase activity in bronchoalveolar lavage fluid of rats (Muller et al, 2008;Sager et al, 2013;Snyder-Talkington et al, 2016a). DOI 10.1002/em evidenced by the dose-dependent elevation in lactate dehydrogenase activity in bronchoalveolar lavage fluid of rats (Muller et al, 2008;Sager et al, 2013;Snyder-Talkington et al, 2016a).…”

“…Moreover, an important number of commonly expressed genes was uniquely identified between the Poulsen et al (2013) and the Snyder-Talkington et al (2016a) studies, probably because they were the ones with the largest transcriptomic dataset, that is, 1,635 and 720 genes, respectively. Moreover, an important number of commonly expressed genes was uniquely identified between the Poulsen et al (2013) and the Snyder-Talkington et al (2016a) studies, probably because they were the ones with the largest transcriptomic dataset, that is, 1,635 and 720 genes, respectively.…”

Pulmonary exposure to cellulose nanocrystals caused deleterious effects to reproductive system in male mice

“…Because of their nanoscale features, inhalable nanomaterials are easily deposited deeper in the lung compared to larger particles (Buzea et al, 2007; Oberdörster et al, 2015). Further, the high aspect ratio of CN along with fibrous nature may impose safety concerns (Shvedova et al, 2014; Cyphert et al, 2016; Snyder-Talkington et al, 2016). …”

Engineered nanomaterial-induced lysosomal membrane permeabilization and anti-cathepsin agents

“…ENM-activation of inflammatory pathways is one of the most studied areas of concern because of the known role for inflammation in many, if not most, chronic and degenerative health diseases (Stephenson et al 2016, Maisch et al 2005, Sethi et al 2012, Kundu and Surh 2008). In addition to inflammation, concerns regarding oxidative stress, pulmonary toxicity, fibrosis, reproductive system, malignant transformations, granuloma formation, and genetic alterations have been raised (Liu et al, 2012; Shvedova et al 2008; Farcas et al, 2016; Schramm et al, 2016; Snyder-Talkington et al, 2016; Chakraborty et al, 2017). …”