Can CuO nanoparticles lead to epigenetic regulation of antioxidant enzyme system?

Chibber, Sandesh; Shanker, Rishi

doi:10.1002/jat.3392

Cited by 26 publications

(15 citation statements)

References 51 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ROS production is one of the harmful responses showing a more significant impact on the alteration of physiology. The occurrence of hepatotoxicity and nephrotoxicity as a result of ROS generation due to NP treatment expected in the present study was from previous studies mentioned in a review by Chibber and Shanker (2017). In the current investigation, MDA levels were significantly increased in the subacute study at a high dose in the treated kidney and brain and at medium as well as high doses of the treated liver, whereas GSH levels showed a significant decrease at high doses in the liver, kidney and brain tissues.…”

Section: Discussionsupporting

confidence: 76%

Acute and subacute oral toxicity of copper oxide nanoparticles in female albino Wistar rats

Bugata

Venkata

Gundu

et al. 2019

J of Applied Toxicology

View full text Add to dashboard Cite

The extensive use of copper oxide nanoparticles (CuO‐NPs) in various industries and their wide range of applications have led to their accumulation in different ecological niches of the environment. This excess exposure raises the concern about its potential toxic effects on various organisms including humans. However, the hazardous potential of CuO‐NPs in the literature is elusive, and it is essential to study its toxicity in different biological models. Hence, we have conducted single acute dose (2000 mg/kg) and multiple dose subacute (30, 300 and 1000 mg/kg daily for 28 days) oral toxicity studies of CuO‐NPs in female albino Wistar rats following OECD guidelines 420 and 407 respectively. Blood analysis, tissue aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and acetylcholinesterase, superoxide dismutase, catalase, lipid malondialdehyde and reduced glutathione assays, and histopathology of the tissues were carried out. The higher dose treatments of the acute and subacute study caused significant alterations in biochemical and antioxidant parameters of the liver, kidney and brain tissues of the rat. In addition, histopathological evaluation of these three organs of treated rats showed significantly high abnormalities in their histoarchitecture when compared to control rats. We infer from the results that the toxicity observed in the liver, kidney and brain of treated rats could be due to the increased generation of reactive oxygen species by CuO‐NPs.

show abstract

Section: Discussionsupporting

confidence: 76%

Acute and subacute oral toxicity of copper oxide nanoparticles in female albino Wistar rats

Bugata

Venkata

Gundu

et al. 2019

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

“…CuO-NPs induced genotoxic responses via the p53 and p38 pathways in A549 lung cells. 11,30,38 CuO-NPs significantly induced DNA damage at 12.5 µg/mL in mouse N2A neuroblastoma cells, with no decrease in cell viability. 28 CuO-NPs induced both cell death and DNA damage in human A549 and BEAS-2B lung epithelial cells via disruption of cell membrane integrity.…”

Section: Discussionmentioning

confidence: 94%

“…37 CuO-NPs induced cell membrane lysis, which leading to necrosis. 29,38 Various combined parameters including endocytosis pathways, presence or absence of specific signaling receptors, mucus or glycocalyx could be affected the cytotoxic response of CuO-NPs in Caco-2 intestinal cells. 19 Titma et al used Resazurin assay and TEER test to evaluate the changes in metabolic activity and permeability in Caco-2 and A549 cell lines (IC25 was 71 µg/mL).…”

Section: Discussionmentioning

confidence: 99%

Cupric Oxide Nanoparticles Induce Cellular Toxicity in Liver and Intestine Cell Lines

2020

View full text Add to dashboard Cite

Purpose: The wide application of cupric oxide nanoparticles (copper (II) oxide, CuO-NPs) in various fields has increased exposure to the kind of active nanomaterials, which can cause negative effects on human and environment health. Although CuO-NPs were reported to be harmful to human, there is still a lack information related to their toxic potentials. In the present study, the toxic potentials of CuO-NPs were evaluated in the liver (HepG2 hepatocarcinoma) and intestine (Caco-2 colorectal adenocarcinoma) cells. Methods: After the characterization of particles, cellular uptake and morphological changes were determined. The potential of cytotoxic, genotoxic, oxidative and apoptotic damage was investigated with several in vitro assays. Results: The average size of the nanoparticles was 34.9 nm, about 2%-5% of the exposure dose was detected in the cells and mainly accumulated in different organelles, causing oxidative stress, cell damages, and death. The IC50 values were 10.90 and 10.04 µg/mL by MTT assay, and 12.19 and 12.06 µg/mL by neutral red uptake (NRU) assay, in HepG2 and Caco-2 cells respectively. Apoptosis assumes to the main cell death pathway; the apoptosis percentages were 52.9% in HepG2 and 45.5% in Caco-2 cells. Comet assay result shows that the highest exposure concentration (20 µg/mL) causes tail intensities about 9.6 and 41.8%, in HepG2 and Caco-2 cells, respectively. Conclusion: CuO-NPs were found to cause significant cytotoxicity, genotoxicity, and oxidative and apoptotic effects in both cell lines. Indeed, CuO-NPs could be dangerous to human health even if their toxic mechanisms should be elucidated with further studies.

show abstract

“…The toxicity of CuO NPs is relatively high when compared with other metal oxide NPs. The negative effects are mostly mediated by ROS production followed by oxidative stress, destruction of mitochondrial membranes and the induction of downstream processes, resulting in autophagy and/or apoptosis [16], including e.g., activation of p53 which increases Bax/Bcl2 ratio. CuO NPs also cause cell cycle arrest and DNA damage manifested by γ-H2AX formation.…”

Section: Discussionmentioning

confidence: 99%

“…They upregulate the expression of DNA repair proteins and directly interact with the structural elements of the cell (e.g., cytoskeleton). This may disrupt the mitotic spindle and cause aberrant cell division [16]. CuO NPs further directly interact with DNA, causing a replication arrest possibly leading to genome instability.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Can CuO nanoparticles lead to epigenetic regulation of antioxidant enzyme system?

Cited by 26 publications

References 51 publications

Acute and subacute oral toxicity of copper oxide nanoparticles in female albino Wistar rats

Acute and subacute oral toxicity of copper oxide nanoparticles in female albino Wistar rats

Cupric Oxide Nanoparticles Induce Cellular Toxicity in Liver and Intestine Cell Lines

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

Contact Info

Product

Resources

About