Intranasal Delivery of Copper Oxide Nanoparticles Induces Pulmonary Toxicity and Fibrosis in C57BL/6 mice

Lai, Xiaofeng; Hu, Zhao; Zhang, Yong; Guo, Kai; Xu, Yuqiao; Chen, Suning; Zhang, Jian

doi:10.1038/s41598-018-22556-7

Cited by 99 publications

(64 citation statements)

References 40 publications

(39 reference statements)

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“…A two-week inhalation period affected the processes associated with apoptosis and programmed cell death. This result is comparable with the observations of Lai et al, who found time-and dose-dependence increased the intensity of the TUNEL-positive cells in the lung sections of mice, after the intranasal delivery of CuO NPs [20]. A six-week exposure period impacted on cell cycle-related processes.…”

Section: Discussionsupporting

confidence: 91%

“…Collagen, the major part of extracellular matrix, is fundamental to maintain the structure and function of the lungs. In a recent study, collagen accumulation, along with the expression of the progressive fibrosis marker α-SMA in the lungs of C57BL/6 mice exposed to CuO NPs by intranasal delivery, was detected [20] suggesting the possible induction of pulmonary fibrosis. Similarly, we also found the upregulation of α-SMA expression.…”

Section: Discussionmentioning

confidence: 95%

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Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles

et al. 2020

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We investigated the transcriptomic response and epigenetic changes in the lungs of mice exposed to inhalation of copper(II) oxide nanoparticles (CuO NPs) (8 × 10 5 NPs/m 3 ) 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.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 95%

Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles

et al. 2020

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“…Augmented collagen production and induction of fibrosis can be associated with activation of myofibroblasts [27,28] and their expression of α-smooth muscle actin (α-SMA) [29]. Previous studies have reported the upregulation of α-SMA expression as a progressive fibrosis marker in the lungs after metal NP exposure [30,31].…”

Section: Figure 3: the Effect Of Pb(no3)2 Np Inhalation And Its Clearmentioning

confidence: 99%

A Clearance Period After Soluble Lead Nanoparticle Inhalation did not Ameliorate the Negative Effects on Target Tissues Due to Decreased Immune Response

Dumková

Smutná

Vrlíková

et al. 2020

Preprint

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Background: The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover possible differences in the effects of lead exposure on individual target organs and to reveal potential variability in the clearance of lead from organs after inhalation of soluble and insoluble lead particles. Mice were exposed to Pb(NO3)2 NPs in whole-body inhalation chambers for up to 11 weeks. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs (lung, liver, kidney, spleen, bone and blood). Results: After exposure to Pb(NO3)2 NPs, the lead concentration was the highest in femur at all designated time points with the exception of 3-day inhalation. In contrast to other organs, the ability to clear the lead from the femur was very low. In the lungs, Pb(NO3)2 NP inhalation induced serious structural changes; lung damage was present even after a 5-week clearance period despite the lead being almost completely eliminated from the lung tissue. Furthermore, in secondary target organs (kidney and liver), Pb(NO3)2 NPs induced several morphological defects, with alterations that remained visible after the clearance period even though the tissue lead concentrations decreased to minimal values. The numbers of lung and liver macrophages were significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, was increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines (tumour necrosis factor alpha [TNF-α], transforming growth factor beta 1 [TGFβ1], interleukin 6 [IL-6], IL-1α and IL-1β) displayed a tissue-specific response to lead exposure. Conclusions: Taken together, diminished inflammatory response in lung and liver after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by enhanced pathological changes in target organs, even after a 5-week clearance period that contrasts to the stronger effect observed previously after the clearance of insoluble lead nanoparticles.

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“…Nanoparticles become a relevant noxious substances and their release from electronic devices and presence in the environment causes a potential risk for humans and lungs are one of the most endangered organs (167). In the recent experiment, toxicity of copper oxide nanoparticles intranasally administered was examined on 57BL/6 mice (168). The used copper nanoparticles induced pulmonary infl ammation resulting in fi brosis.…”

Section: Copper Nanoparticlesmentioning

confidence: 99%

Copper and copper nanoparticles toxicity and their impact on basic functions in the body

Pohanka¹

2019

BLL

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Copper is a biogenic metal having multiple functions in basic processes in organisms and it is common in all kingdoms of life. Limited intake of copper is a problem; however, doses of copper exceeding the recommended alimentary source are problematic as well and toxicity is soon manifested. Impact of copper nanoparticles on human health is another serious issue taken into consideration in this review. Regarding to copper toxicity, neurodegenerative disorders including Alzheimer and Parkinson diseases are suspected to be linked to copper toxicity or copper can contribute to their progression. Wilson and Menke diseases are also described as examples of copper intolerance. This paper is focused on the description, literature survey and discussion of the current knowledge about copper and copper nanoparticles toxicity and their involvement in various pathological processes (Tab. 6, Fig. 2, Ref. 171).

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Intranasal Delivery of Copper Oxide Nanoparticles Induces Pulmonary Toxicity and Fibrosis in C57BL/6 mice

Cited by 99 publications

References 40 publications

Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles

Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles

A Clearance Period After Soluble Lead Nanoparticle Inhalation did not Ameliorate the Negative Effects on Target Tissues Due to Decreased Immune Response

Copper and copper nanoparticles toxicity and their impact on basic functions in the body

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