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Total nucleated cells (A), macrophages (B), neutrophils (C), and lymphocytes (D) in PCLFs following exposure of rats to vehicle controls, SWCNTs (SW-L or SW-H), or MWCNTs (MW-L or MW-H) at the indicated time points. The resulting values were analyzed by comparing data from the treated and vehicle control groups by Dunnett's procedure based on the re-sampling method ( * p < 0.05, ** p < 0.01), after the data were found to be non-homogeneous by Bartlett's test for homogeneity of distribution (p < 0.20).
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Relationships between the physical properties of carbon nanotubes (CNTs) and their toxicities have been studied. However, little research has been conducted to investigate the pulmonary and pleural inflammation caused by short-fiber single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs). This study was performed to characterize differences in r...
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... Furthermore, we believe that analyzing the intensity of the effects exhibited by the test material immediately after its administration, as well as observing the subsequent increase or decrease of these effects during the rearing period, can offer valuable information about the toxicity profile of the individual test material. In our research, we have also employed intratracheal instillation to assess the pulmonary toxicity of CNFs, CNTs, or carbon fibers [8][9][10]13,14,19,27]. Based on these findings, we hypothesized that by evaluating the extent to which pulmonary inflammation induced by CNFs or MWCNTs subsides or persists, we could discern the differing adverse effects of each material. ...
This study assessed the effects of cellulose nanofibrils (CNFs) and multi-walled carbon nanotubes (MWCNTs) on lung inflammation in a cigarette smoke-induced chronic obstructive pulmonary disease (COPD) mouse model. Prior to instillation, COPD model mice displayed distinctive cellular compositions and elevated cytokine levels in bronchoalveolar lavage fluid (BALF). After intratracheal instillation of 80 μg CNFs, no significant histopathological changes, BALF composition alterations, or cytokine level shifts were observed on day 28. This suggests minimal lung impact and no interference with reducing smoke-induced inflammation. In contrast, the instillation of 80 μg MWCNTs resulted in significant histopathological changes, increased cellular composition, and elevated cytokine levels in BALF on day 28. These findings indicate that CNF exposure had little effect on the lungs and did not impede the reduction of smoke-induced inflammation, while MWCNT exposure hindered the attenuation of pulmonary inflammatory response. The study emphasizes the importance of considering diverse cases, including individuals with pre-existing respiratory conditions, when assessing occupational safety and health risks associated with advanced nanomaterial exposure.
... Endocytosis is typically used to internalize CNTs. Inflammation in the pulmonary system after exposure to short SWMCNTs (Single-walled carbon nanotubes) and MWCNTs (Multi-walled carbon nanotubes) was examined by Fujita et al. in 2016 [27]. ...
In order to tackle multifactorial illnesses, the importance of bioactive peptides in nano drug delivery systems is emphasised. Multifactorial diseases are primarily brought on by protein misfolding. Therefore, pharmaceutical formulations are recommended to deliver a successful treatment. Difficulties hinder its application in delivering raw peptides with poor bioavailability, absorption , and circulation time, making it a difficult assignment for researchers. Recently, bioactive pep-tides have become increasingly important in therapy. In addition, several bioactive proteins have poor absorption characteristics in the GIT. These issues can be resolved by creating nano-based peptide-based delivery systems that encapsulate, retain, protect, and transport bioactive peptides. The focus of the proposed review paper is to provide an overview of peptides, commercialization concerns, and their related attempts to develop into novel peptide-based nanoformulations.
... For example, C57BL/6 mice exposed via a single intratracheal instillation to 18, 54, and 162 µg/mouse of long or short MWCNTs only resulted in strong inflammatory and fibrotic responses in mouse lungs exposed to long MWCNTs on day 28 post-exposure, suggesting that fiber length may be associated with stronger lung inflammatory and lung fibrotic responses [10]. In Wistar rats, the intratracheal instillation of 0.15 or 1.5 mg/kg of SWCNTs induced persistent pulmonary inflammation on day 90 post-exposure, whereas the highest dose of MWCNTs induced acute inflammatory responses on days 1 and 3 post-exposure, which resolved overtime [11], suggesting the number of walls is important for the tubes' toxicity. In addition to length and wall number, surface functionalization also plays a role in the toxicity of CNTs. ...
Single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) are nanomaterials with one or multiple layers of carbon sheets. While it is suggested that various properties influence their toxicity, the specific mechanisms are not completely known. This study was aimed to determine if single or multi-walled structures and surface functionalization influence pulmonary toxicity and to identify the underlying mechanisms of toxicity. Female C57BL/6J BomTac mice were exposed to a single dose of 6, 18, or 54 μg/mouse of twelve SWCNTs or MWCNTs of different properties. Neutrophil influx and DNA damage were assessed on days 1 and 28 post-exposure. Genome microarrays and various bioinformatics and statistical methods were used to identify the biological processes, pathways and functions altered post-exposure to CNTs. All CNTs were ranked for their potency to induce transcriptional perturbation using benchmark dose modelling. All CNTs induced tissue inflammation. MWCNTs were more genotoxic than SWCNTs. Transcriptomics analysis showed similar responses across CNTs at the pathway level at the high dose, which included the perturbation of inflammatory, cellular stress, metabolism, and DNA damage responses. Of all CNTs, one pristine SWCNT was found to be the most potent and potentially fibrogenic, so it should be prioritized for further toxicity testing.
... In mice, it has been suggested that the uptake of SWCNTs by macrophages activates transcription factors that lead to oxidative stress, inflammation, and severe pulmonary granuloma formation (0.5 mg) [116]. It is important to note that SWCNTs and MWCNTs display pulmonary toxicity [117]. ...
... Another study has also reported positive outcomes in soil microorganisms exposed to low doses of carbon nanotubes [199]. However, other model organisms have shown negative effects from exposure to similar doses of carbon nanotubes [111,113,114,[116][117][118][119][120]. ...
Biosensors often combine biological recognition elements with nanomaterials of varying compositions and dimensions to facilitate or enhance the operating mechanism of the device. While incorporating nanomaterials is beneficial to developing high-performance biosensors, at the stages of scale-up and disposal, it may lead to the unmanaged release of toxic nanomaterials. Here we attempt to foster connections between the domains of biosensors development and human and environmental toxicology to encourage a holistic approach to the development and scale-up of biosensors. We begin by exploring the toxicity of nanomaterials commonly used in biosensor design. From our analysis, we introduce five factors with a role in nanotoxicity that should be considered at the biosensor development stages to better manage toxicity. Finally, we contextualize the discussion by presenting the relevant stages and routes of exposure in the biosensor life cycle. Our review found little consensus on how the factors presented govern nanomaterial toxicity, especially in composite and alloyed nanomaterials. To bridge the current gap in understanding and mitigate the risks of uncontrolled nanomaterial release, we advocate for greater collaboration through a precautionary One Health approach to future development and a movement towards a circular approach to biosensor use and disposal.
... However, in one study, the MWCNT-induced inflammatory responses in the pleural cavity and hyperplastic visceral mesothelial proliferation could have been affected by the short experimental period (15). It was found in other research that SWCNTs with a length of 0.5 µm were able to induce similar inflammatory effects as seen with MWCNTs (85). ...
Carbon nanotubes (CNTs) are nanomaterials with broad applications that are produced on a large scale. Animal experiments have shown that exposure to CNTs, especially one type of multi-walled carbon nanotube, MWCNT-7, can lead to malignant transformation. CNTs have characteristics similar to asbestos (size, shape, and biopersistence) and use the same molecular mechanisms and signaling pathways as those involved in asbestos tumorigenesis. Here, a comprehensive review of the characteristics of carbon nanotubes is provided, as well as insights that may assist in the design and production of safer nanomaterials to limit the hazards of currently used CNTs.
... The current data pertains to MWCNT. A question is whether they can be While short MWCNTs had a more immediate and larger impact on the alveoli that had J o u r n a l P r e -p r o o f shorter duration than the SWCNT (Fujita et al., 2016). Honda et al. compared short (0.6 µm) and long (8.6 µm) SWCNTs by intratracheal instillation into rats at 0.2 and 1 mg/kg bw (long) and 1 mg/kg bw (short). ...
Potentially, the toxicity of multiwalled carbon nanotubes (MWCNTs) can be reduced in a safe-by-design strategy. We investigated if genotoxicity and pulmonary inflammation of MWCNTs from the same batch was lowered by a) reducing length and b) introducing COOH-groups into the structure. Mice were administered: 1) long and pristine MWCNT (CNT-long) (3.9 µm); 2) short and pristine CNT (CNT-short) (1 µm); 3) CNT modified with high ratio COOH-groups (CNT-COOH-high); 4) CNT modified with low ratio COOH-groups (CNT-COOH-low). MWCNTs were dosed by intratracheal instillation at 18 or 54 µg/mouse (∼0.9 and 2.7 mg/kg bw). Neutrophils numbers were highest after CNT-long exposure, and both shortening the MWCNT and addition of COOH-groups lowered pulmonary inflammation (day 1 and 28). Likewise, CNT-long induced genotoxicity, which was absent with CNT-short and after introduction of COOH groups. In conclusion, genotoxicity and pulmonary inflammation of MWCNTs were lowered, but not eliminated, by shortening the fibres or introducing COOH-groups.
... Such tests are simpler and use smaller amounts of test material in comparison with inhalation exposure test. Moreover, dose to the lungs can be determined precisely, and intratracheal instillation has been used for evaluating the toxicity of several nanomaterials (Kobayashi et al. 2019;Fujita et al. 2016;Honda et al. 2017). We believe that the intratracheal instillation using test material dispersed in liquid is appropriate for evaluating CNF dispersed in an aqueous solvent. ...
... It has been reported that CNTs administered to the lungs may pass through the pleura and translocate through lymphatic drainage in the thoracic cavity to the mediastinal lymph nodes (Murphy et al. 2011). In addition, we have observed using TEM that SWCNTs and MWCNTs are localized in the mediastinal lymph nodes following intratracheal instillation (Fujita et al. 2015(Fujita et al. , 2016Honda et al. 2017). This study demonstrated that the blackening of mediastinal lymph nodes was observed in one case for each MWCNT dose group on day 90. ...
... Our results demonstrate that acute inflammation induced by MWCNTs was not attenuated by day 90 post-instillation, in contrast to attenuation of inflammation following CNF instillation. Several studies on the pulmonary toxicity of MWCNTs using in vivo rodent models are available (Kasai et al. 2016;Morimoto et al. 2012;Pauluhn 2010;Muller et al. 2005;Fujita et al. 2016). A 90-day inhalation toxicity study was performed with the same Nanocyl NC7000 TM MWCNT material used in this study. ...
Safety assessment of cellulose nanofibrils (CNFs) is required to accelerate the utilization of these materials in industrial applications. The present study aimed to characterize the effects on rat pulmonary inflammation over a period of 90 days following intratracheal instillation of three types of CNFs or multi-walled carbon nanotubes (MWCNTs) at doses of 0.5, 1.0, or 2.0 mg/kg. The pulmonary inflammatory responses induced by phosphorylated CNFs (CNF1), 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized CNFs (CNF2), CNFs produced via mechanical defibrillation (CNF3), and MWCNTs were investigated using bronchoalveolar lavage fluid analysis, histopathological findings, and comprehensive gene expression profiling of rat lungs. CNF1 and CNF2 with approximately equal diameter (7.0–8.0 nm) and length (0.8–1.0 µm) distributions induced inflammation after dosing, which was attenuated 90 days post-instillation. CNF3 of relatively greater thickness (21.2 nm) and longer length (1.7 μm) deposited around the terminal bronchioles were observed after instillation. Acute inflammatory responses in the alveoli induced by CNF3 were mild compared with those induced by other materials and attenuated 90 days post-instillation. MWCNTs induced severe pulmonary inflammatory responses that continued during the test period. The inflammation failed to resolve within 90 days post-instillation. A hierarchical cluster analysis revealed comparable gene expression profiles for CNF1, CNF2, and CNF3, whereas profiles of MWCNTs were different from those of other test substances. This study suggests that pulmonary inflammation is associated with the diameter and length distributions of CNFs and that the pulmonary inflammation caused by CNFs is mild compared with that caused by MWCNTs.
Graphic abstract
... For example, when an atopic dermatitis mouse model, a mast cell specific pathology, was co-exposed to allergen and the non-IgE agonist silver nanoparticles (AgNP), there were significantly worsened symptoms than allergen alone [45]. Also, IL-33 activation of mast cells in the lung plays a prominent role in the initiation and development of airway hyper-responsiveness and pulmonary inflammation [46][47][48]. Many common mast cell agonists activate through non-IgE receptors (e.g., adverse drug allergies, complement, and neuropeptides). ...
Mast cells are essential first responder granulocytes in the innate immune system that are well known for their role in type 1 immune hypersensitivity reactions. Although mostly recognized for their role in allergies, mast cells have a range of influences on other systems throughout the body and can respond to a wide range of agonists to properly prime an appropriate immune response. Mast cells have a dynamic energy metabolism to allow rapid responsiveness to their energetic demands. However, our understanding of mast cell metabolism and its impact on mast cell activation and development is still in its infancy. Mast cell metabolism during stimulation and development shifts between both arms of metabolism: catabolic metabolism—such as glycolysis and oxidative phosphorylation—and anabolic metabolism—such as the pentose phosphate pathway. The potential for metabolic pathway shifts to precede and perhaps even control activation and differentiation provides an exciting opportunity to explore energy metabolism for clues in deciphering mast cell function. In this review, we discuss literature pertaining to metabolic environments and fluctuations during different sources of activation, especially IgE mediated vs. non-IgE mediated, and mast cell development, including progenitor cell types leading to the well-known resident mast cell.
... The administration of SWCNts in mice (Mus musculus) caused damage to mitochondria and cellular apoptosis due to the accumulation of these CNTs in the lungs, spleen, and kidneys (Principi et al. 2016). Fujita et al. (2016) administered doses of SWCNTs and MWCNTs in Rattus novergicus (rat) and observed pleural and pulmonary inflammation. ...
According to literature consensus, nanoparticles are particulate material either engineered or produced naturally, with at least one dimension of 100 nm or less. Currently, an absurd quantity of nanoparticles has been produced with the most different purposes. The establishment of nanoparticles capable of interacting with biological systems in a predictable and controlled way has enabled the development of unprecedented techniques called nanomedicine. The nanomedicine has revolutionized the medical sciences by introducing new diagnostics and treatments at the frontier of knowledge. Such a revolution was possible by varying shapes, sizes, and surfaces of nanoparticles formed by different materials. However, nanoparticles’ use comes along with the risk of potentially adverse effects in natural systems. The increasing application of nanoparticles, both quantitatively and by product diversity, will lead to a diversification in emission sources into the environment. The interaction of particles, which eventually reach the environment, with the biological systems still lacks detailed studies. Therefore, understanding the effect and mechanism of nanoparticle cell interactions, and consequent cellular responses, requires a careful examination including morphological and biochemical aspects. In this chapter, we will discuss basic aspects of nanoparticles interaction in biological systems regarding their application in nanomedicine as well as the potentially unwanted interactions when this nanostructured material is dumped into the environment as an environmental pollutant.
... Langley et al. found that CCL2 and CCL7 were persistently upregulated in rat lungs that were exposed to inhaled crystalline silica, a dust with high toxicity [43]. Fujita et al. also reported that CCL2 and CCL7 were upregulated in the lungs of rats injected intratracheally with inflammogenetic single-wall carbon nanotube (SWCNT) [38,44]. Abdelgied et al. found that CCL2 expression was increased in rat lungs following intratracheal instillation of potassium octatitanate fibers (POT fibers), which are suggested to have carcinogenic potential [45]. ...
We analyzed the mRNA expression of chemokines in rat lungs following intratracheal instillation of nanomaterials in order to find useful predictive markers of the pulmonary toxicity of nanomaterials. Nickel oxide (NiO) and cerium dioxide (CeO2) as nanomaterials with high pulmonary toxicity, and titanium dioxide (TiO2) and zinc oxide (ZnO) as nanomaterials with low pulmonary toxicity, were administered into rat lungs (0.8 or 4 mg/kg BW). C-X-C motif chemokine 5 (CXCL5), C-C motif chemokine 2 (CCL2), C-C motif chemokine 7 (CCL7), C-X-C motif chemokine 10 (CXCL10), and C-X-C motif chemokine 11 (CXCL11) were selected using cDNA microarray analysis at one month after instillation of NiO in the high dose group. The mRNA expression of these five genes were evaluated while using real-time quantitative polymerase chain reaction (RT-qPCR) from three days to six months after intratracheal instillation. The receiver operating characteristic (ROC) results showed a considerable relationship between the pulmonary toxicity ranking of nanomaterials and the expression of CXCL5, CCL2, and CCL7 at one week and one month. The expression levels of these three genes also moderately or strongly correlated with inflammation in the lung tissues. Three chemokine genes can be useful as predictive biomarkers for the ranking of the pulmonary toxicity of nanomaterials.
