Similar pulmonary toxicity and gene expression changes after short-term inhalation exposure to surface-modified copper oxide nanoparticles
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE158900 | GEO | 2020/10/02
REPOSITORIES: GEO
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Project description:The in vitro and in vivo toxicity of copper oxide nanoparticles (CuO NPs) is attributed to both particle and dissolved copper ion species. However, a clear understanding of 1) the specific cellular responses that are modulated by the two species and 2) the temporal dynamics in toxicity, as the proportional amount of particulate and ionic forms change over time, is lacking. In the current study, in vitro responses to microparticulate CuO (CuO MPs), CuO NPs, and dissolved Cu2+ were characterized in order to elucidate particle and ion induced kinetic effects. Particle dissolution experiments were carried out in relevant cell culture medium, using CuO NPs and MPs. Mouse lung epithelial cells were exposed for 2 - 48 h with 1 - 25 µg/mL CuO MPs, CuO NPs, or 7 & 54 µg/mL CuCl2. Cellular viability and genome-wide transcriptional responses were assessed. Dose and time dependent cytotoxicity was observed in CuO NP exposed cells, which was delayed and subtle in CuCl2 and not observed in CuO MPs treated cells. Analyses of differentially expressed genes and associated pathway perturbations showed that dissolved ions released by CuO NPs in extracellular medium are insufficient to account for the observed potency and cytotoxicity. Further organization of gene expression results in an Adverse Outcome Pathway (AOP) framework revealed a series of key events potentially involved in CuO NPs toxicity. The AOP is applicable to soluble metal oxide nanoparticle induced toxicity in general, and thus, can facilitate the development of in vitro alternative strategies to screen their toxicity.
2022-11-03 | GSE161017 | 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: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: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:Purpose: The intensive use of metal-based nanoparticles results in their continuous release into the environment and the subsequent destroying microbial biodiversity and causing occurrence of antibiotic resistant determinants. Although previous studies have indicated that nanoparticles may be toxic to microorganisms, there is a scarcity of data available to assess the underlying molecular mechanisms of inhibitory and biocidal effects of nanoparticles on microorganisms, which is a critical gap in our comprehensive understanding of the impacts of nanoparticles on microbial ecosystems. Methods: By combining the global activated/suppressed gene profiles and detected physiological responses, we detected the microbial response to CuO NPs exposure and revealed potential mechanisms of CuO NPs on this prevalent opportunistic pathogen and environmentally relevant denitrifier. Results:Our results indicate that nanoparticles could react directly with the biological membrane, but also change gene expressions. Transmission electron microscopy (TEM) results indicate that CuO nanoparticles not only damaged the structure of the bacterial membrane but also entered the cells. Planktonic cells of P. aeruginosa are energetically compromised after exposure to a sublethal level (1 and 10 mg/L) of CuO nanoparticles. Respiration was likely inhibited as denitrification activity was severely depleted in terms of decreased transcript levels of most denitrification genes. In addition, and of high concern, bacteriophage genes were activated and it is speculated that phage mediated cell lysis. Meanwhile, CuO NP exposure induced significantly up-regulated expressions of metal resistance gene, resistance-nodulation-division, P-type ATPase efflux and cation diffusion facilitator transporters, which can form an integrated network controlling metals concentrations in the cytoplasm and periplasm P. aeruginosa. Conclusion: Based on our results, it is evident that the response of bacteria under the exposure of nanoparticles is very complex, though a clear and comprehensive understanding of the true mechanisms of inhibition or toxicity is still lacking. Our findings will provide insights on whole picture regarding the fundamental mechanisms of microbial susceptibility, tolerance and resistance to exposure of CuO NPs, as well highlight to re-estimate potential risks of CuO NP to public health and environment.
2017-12-31 | GSE99981 | GEO
Project description:In this work we study the pulmonary toxicological properties of titanium dioxide using conventional and molecular toxicological approaches. For this, we exposed Fischer 344 rats by nose-only inhalation 6 hours/day, 5 days/week for 4 weeks to a nanoaerosol of TiO2 (10 mg/m3). Lung samples have been collected up to 180 days after the end of exposure. Biochemical and cytological analyses of the broncho-alveolar lavage fluid (BALF) were performed. In addition, transcriptomic and proteomic approaches were realised in the lung and BALF respectively.
2019-01-17 | GSE99997 | GEO
Project description:Purpose: The objective of this study is to reveal the potential effects of CuO nanoparicles (NPs) on Desulfovibrio vulgaris Hildenborough (D. vulgaris) via genome-wide RNA sequencing Methods: RNA was harvested from D. vulgaris cultures in the presence and absence of CuO NPs (0, 1, 50, 250 mg CuO NPs/L) 8 h after cultivation.
2019-08-01 | GSE101911 | GEO
Project description:Silver nanoparticles (NPs) are extensively used due to their antimicrobial activity and, therefore, their input into the ecosystem will increase. Silver can be bioaccumulated by low trophic level organisms and, then, incorporated into the food chain, reaching high level predators. The objectives of this study were to test the acute toxicity of N-vynil-2-pirrolidone/polyethylenimine (PVP-PEI) coated Ag NPs of 5 nm to brine shrimp (Artemia sp) larvae and to assess bioaccumulation and effects of silver transferred by the diet. For the later, brine shrimps were exposed to two different concentrations of Ag NPs, 100 ng/L as an environmentally relevant concentration and 100 µg/L as a likely effective concentration, in parallel with an unexposed control group and, then, used to feed zebrafish during 21 days in order to simulate two trophic levels of a simplified food web. For brine shrimp larvae, EC50 values ranged from 7.39 mg Ag/L (48 h post hatch larvae (hph) exposed for 48 h) to 19.63 mg Ag/L (24 hph larvae exposed for 24 h. Silver accumulation was measured in brine shrimps exposed to 0.1 and 1 mg/L of Ag NPs for 24 h. In zebrafish fed with brine shrimps exposed to Ag NPs, intestine showed higher metal accumulation than liver, although both organs presented the same pattern of dose and time-dependent metal accumulation as revealed by autometallography. Feeding of zebrafish for 3 days with brine shrimps exposed to 100 ng/L of Ag NPs was enough to impair fish health as reflected by the significant reduction of the lysosomal membrane stability and the presence of several histopathological conditions in the liver. Overall, results showed that Ag NPs were able to exert toxic effects on zebrafish through dietary exposure, even at an environmentally relevant concentration, which should act as concern of the need of studies in further detail about real impact of nanomaterials in the environment.
2017-03-21 | GSE90457 | GEO
Project description:The present research aimed to investigate peripheral blood gene expression profiling as a minimally invasive surrogate approach to study silica-induced pulmonary toxicity. Rats were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days). Pulmonary damage and blood gene expression profiles were determined at various latency periods (0 - 16 weeks). Silica exposure resulted in pulmonary toxicity and this was evidenced by histological changes in the lungs and elevation of LDH activity, and total protein and albumin contents in the bronchoalveolar lavage fluid (BALF) of the rats. Microarray analysis of global gene expression profiles in the blood of the rats identified genes that were differentially expressed in response to silica exposure and toxicity. The number of significantly differentially expressed genes in the blood of silica exposed rats correlated with the severity of silica-induced pulmonary toxicity. Genes involved in biological functions such as inflammatory response, cancer, pulmonary damage, oxidative stress, energy metabolism, fibrosis, etc, were found differentially expressed in the blood of the silica exposed rats compared with the controls. Induction of pulmonary inflammation in the silica exposed rats, as suggested by differential expression of inflammatory response genes in the blood, was supported by significant increases in the number of macrophages and infiltrating neutrophils as well as the activity of pro-inflammatory chemokines M-bM-^@M-^S MCP1 and MIP2, observed in the BALF of the silica exposed rats. A silica-responsive blood gene expression signature developed using the gene expression data predicted with significant accuracy the exposure of rats to lower concentrations (1 and 2 mg/m3) of silica. Taken together our findings suggest the potential application of peripheral blood gene expression profiling as a minimally invasive and efficient surrogate approach to detect and study silica-induced pulmonary toxicity. 96 samples were analyzed in this experiment. The RNA from rat blood samples was isolated for gene expression studies. Rats (48) were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days) and air (24). Blood gene expression profiling was performed using rat blood samples, 8 each for silica exposed and 4 each for air exposed controls at various post-exposure time periods (0, 1, 2, 4, 8, and 16 weeks). A silica-responsive blood gene expression signature was developed using the gene expression data obtained from the 0 week post-exposure group and the control rats. The signature was tested for predicting silica exposure and resulting toxicity in the rats exposed to lower concentrations (1 and 2 mg/m3) of silica (8 rats per group) and air (8 rats).
2011-12-02 | E-GEOD-27023 | biostudies-arrayexpress
