Similar pulmonary toxicity and gene expression changes after short-term inhalation exposure to surface-modified copper oxide nanoparticles
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PROVIDER: PRJNA666921 | ENA |
REPOSITORIES: ENA
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Project description:This study investigated the pulmonary toxicity of Copper oxide nanoparticles (CuO NPs) surface modified with polyethylenimine (PEI) or ascorbate (ASC), was investigated. Rats were exposed nose-only to a fixed exposure concentration of ASC or PEI coated CuO NPs for 5 consecutive days. On day 6 and day 27 post-exposure, pulmonary toxicity markers in bronchoalveolar lavage fluid (BALF) were analyzed and histopathological evaluation of the lungs was performed, along with microarray analyses on whole lung tissue samples.
2020-10-02 | GSE158900 | GEO
Project description:Copper oxide nanoparticles (CuO NPs) are considered for various technological and consumer applications, leading to growing concerns for potential human hazards resulting from inhalation. Recent studies have revealed a dose-dependent toxicity of CuO NPs in rats following short-term inhalation exposure. Here, we utilized transcriptomics approaches to further investigate the responses in rats exposed via inhalation for five consecutive days to two doses of CuO NPs, 3.3 (low dose, LD) and 13.2 (high dose, HD) mg/m3, with collection of lung tissues on days 6 (1 day post-exposure) and 28 (i.e., after a 22-day post-exposure recovery period). Histopathology confirmed an acute inflammatory response that was resolved during the post-exposure phase. Global gene expression analyses yielded about 1,000 differentially expressed genes in HD rats and 200 in LD on day 6, and less than 20 after the recovery period. Pathway analysis indicated cell proliferation/survival and inflammation as the main processes triggered by exposure and identified epithelial cell transforming protein 2 (Ect2) as a potential gene of interest implicated in cell proliferation. Indeed, ECT2 was upregulated in exposed lungs and was localized in the cytoplasm of alveolar epithelial cells in HD rats, in hyperplasic foci identified based on the Ki67 antigen, a marker of cell proliferation. Monocyte chemoattractant protein 1 (MCP-1, also known as CCL2), with an important role in the regulation of inflammatory processes and cell proliferation, was also upregulated and this was confirmed immunohistochemically. Finally, we could not find any evidence for aberrant DNA methylation of inflammation-associated genes in response to CuO NP exposure. In summary, the current findings suggest that airborne CuO NPs cause an acute response that translates into inflammation and cellular proliferation in bronchoalveolar epithelium, with upregulation of neoplasia-related factors even after a short-term exposure.
2018-09-01 | GSE86390 | GEO
Project description:To identify the molecular impact of SPIO nanoparticle inhalation exposure on lung tissue. Transcriptional responses were measured by global microarray analysis of mouse lung. Male Balb/c mice were exposed to aerosolized SPIO nanoparticles using a nano-aerosol generation and inhalation system . Exposure was performed using two groups of 30 male Balb/c mices (60 total). One group of 30 was exposed to aerosolized SPIO nanopartic
2014-04-15 | E-GEOD-51417 | biostudies-arrayexpress
Project description:Inhalation and low-dose aspiration elicit highly similar pulmonary inflammation which was confirmed by activation of essentially similar biological pathways and even the same genes. Present results provide evidence that oropharyngeal aspiration is valid approach for hazard assessment of nanomaterials and proper alternative method for inhalation exposure.
2017-05-01 | GSE85711 | GEO
Project description:This study proposes a molecular mechanism for lung epithelial A549 cell response to copper oxide nanoparticles (CuO-NPs) related to Cu ions released from CuO-NPs. Cells that survived exposure to CuO-NPs arrested the cell cycle as a result of the downregulation of proliferating cell nuclear antigen (PCNA), cell division control 2 (CDC2), cyclin B1 (CCNB1), target protein for Xklp2 (TPX2), and aurora kinase A (AURKA) and B (AURKB). Furthermore, cell death was avoided through the induced expression of nuclear receptors NR4A1 and NR4A3 and growth arrest and DNA damage-inducible 45 β and γ (GADD45B and GADD45G, respectively). The downregulation of CDC2, CCNB1, TPX2, AURKA, and AURKB, the expressions of which are involved in cell cycle arrest, was attributed to Cu ions released from CuO-NPs into medium. NR4A1 and NR4A3 expression was also induced by Cu ions released into the medium. The expression of GADD45B and GADD45G activated the p38 pathway that was involved in escape from cell death. The upregulation of GADD45B and GADD45G was not observed with Cu ions released into medium but was observed in cells exposed to CuO-NPs. However, because the expression of the genes was also induced by Cu ion concentrations higher than that released from CuO-NPs into the medium, the expression appeared to be triggered by Cu ions released from CuO-NPs taken up into cells. We infer that, for cells exposed to CuO-NPs, those able to make such a molecular response survived and those unable to do so eventually died. Two-condition experiment, CuO-NPs exposured vs. non-treated cells. Hybridization: 2 replicates. Scanning: 3 replicates (Gain changed).
2012-01-05 | E-GEOD-33278 | biostudies-arrayexpress
Project description:This study proposes a molecular mechanism for lung epithelial A549 cell response to copper oxide nanoparticles (CuO-NPs) related to Cu ions released from CuO-NPs. Cells that survived exposure to CuO-NPs arrested the cell cycle as a result of the downregulation of proliferating cell nuclear antigen (PCNA), cell division control 2 (CDC2), cyclin B1 (CCNB1), target protein for Xklp2 (TPX2), and aurora kinase A (AURKA) and B (AURKB). Furthermore, cell death was avoided through the induced expression of nuclear receptors NR4A1 and NR4A3 and growth arrest and DNA damage-inducible 45 β and γ (GADD45B and GADD45G, respectively). The downregulation of CDC2, CCNB1, TPX2, AURKA, and AURKB, the expressions of which are involved in cell cycle arrest, was attributed to Cu ions released from CuO-NPs into medium. NR4A1 and NR4A3 expression was also induced by Cu ions released into the medium. The expression of GADD45B and GADD45G activated the p38 pathway that was involved in escape from cell death. The upregulation of GADD45B and GADD45G was not observed with Cu ions released into medium but was observed in cells exposed to CuO-NPs. However, because the expression of the genes was also induced by Cu ion concentrations higher than that released from CuO-NPs into the medium, the expression appeared to be triggered by Cu ions released from CuO-NPs taken up into cells. We infer that, for cells exposed to CuO-NPs, those able to make such a molecular response survived and those unable to do so eventually died.
2012-01-05 | GSE33278 | GEO
Project description:Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects in the airways following inhalation. In the present study, the acute (24?h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60?min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited doses in the upper and lower respiratory tracts were calculated. Endpoints were acute airway irritation, pulmonary inflammation based on analyses of bronchoalveolar lavage (BAL) cell composition, DNA damage assessed by the comet assay and pulmonary toxicity assessed by protein level in BAL fluid and histology. All studied particles reduced the tidal volume in a concentration-dependent manner accompanied with an increase in the respiratory rate. In addition, ZnO and TiO2 induced nasal irritation. BAL cell analyses revealed both neutrophilic and lymphocytic inflammation 24-h post-exposure to all particles except TiO2. The ranking of potency regarding induction of acute lung inflammation was Al2O3 = TiO2?<?CeO2 ? ZnO. Exposure to CeO2 gave rise to a more persistent inflammation; both neutrophilic and lymphocytic inflammation was seen 13 weeks after exposure. As the only particles, ZnO caused a significant toxic effect in the airways while TiO2 gave rise to DNA-strand break as shown by the comet assay.
| S-EPMC5020351 | biostudies-literature
Project description:Inhalation is a major nanoparticle exposure pathway. Following inhalation, nanoparticles first interact with the lung lining fluid, a complex mixture of proteins, lipids, and mucins. We measure the concentration and composition of lung fluid proteins adsorbed on the surface of titanium dioxide (TiO2) nanoparticles. Using proteomics, we find that lung fluid results in a unique protein corona on the surface of the TiO2 nanoparticles.
2023-11-10 | PXD041036 | Pride
Project description:We investigated the transcriptomic response and epigenetic changes in the lungs of mice exposed to inhalation of copper(II) oxide nanoparticles (CuO NPs) (8 × 105 NPs/m3) for periods of 3 days, 2 weeks, 6 weeks, and 3 months. A whole genome transcriptome and miRNA analysis was performed using next generation sequencing. Global DNA methylation was assessed by ELISA. The inhalation resulted in the deregulation of mRNA transcripts: we detected 170, 590, 534, and 1551 differentially expressed transcripts after 3 days, 2 weeks, 6 weeks, and 3 months of inhalation, respectively. Biological processes and pathways affected by inhalation, differed between 3 days exposure (collagen formation) and longer treatments (immune response). Periods of two weeks exposure further induced apoptotic processes, 6 weeks of inhalation affected the cell cycle, and 3 months of treatment impacted the processes related to cell adhesion. The expression of miRNA was not affected by 3 days of inhalation. Prolonged exposure periods modified miRNA levels, although the numbers were relatively low (17, 18, and 38 miRNAs, for periods of 2 weeks, 6 weeks, and 3 months, respectively). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis based on miRNA-mRNA interactions, revealed the deregulation of processes implicated in the immune response and carcinogenesis. Global DNA methylation was not significantly affected in any of the exposure periods. In summary, the inhalation of CuO NPs impacted on both mRNA and miRNA expression. A significant transcriptomic response was already observed after 3 days of exposure. The affected biological processes and pathways indicated the negative impacts on the immune system and potential role in carcinogenesis.
| S-EPMC7153614 | biostudies-literature
Project description:Nickel oxide nanoparticles (NiO NPs) have been the focus of many toxicity studies. However, acute toxicity studies that identify toxicological dose descriptors, such as an LC50 or LD50, are lacking. In this paper, the acute toxicity of NiO NPs was evaluated in albino-derived Sprague-Dawley rats through OECD guideline studies conducted by both the oral and inhalation routes of exposure. The animals were assessed for mortality, body weight, behavioral observations, and gross necropsy. Results from previously conducted (unpublished) acute inhalation studies with larger NiO microparticles (MPs) are also included for comparison. Mortality, the primary endpoint in acute toxicity studies, was not observed for rats exposed to NiO NPs via either the oral or inhalation exposure routes, with a determined LD50 of >5000 mg/kg and an LC50 > 5.42 mg/L, respectively. Our results suggest that these NiO NPs do not exhibit serious acute toxicity in rats or warrant an acute toxicity classification under the current GHS classification criteria. This aligns with similar results for NiO MPs from this and previously published studies.
| S-EPMC9860552 | biostudies-literature