Low-dose exposure of silica nanoparticles induces cardiac dysfunction via neutrophil-mediated inflammation and cardiac contraction in zebrafish embryos

Duan, Junchao; Yu, Yang; Li, Yang; Li, Yanbo; Liu, Hongcui; Li, Jing; Yang, Man; Wang, Ji; Li, Chunqi; Sun, Zhiwei

doi:10.3109/17435390.2015.1102981

Cited by 124 publications

(62 citation statements)

References 45 publications

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“…Increased level of hsp90aa1.2 was observed in zebrafish exposed to site H4 water, consistent with the results that the expression levels of various hsp genes are increased in fish exposed to environmental pollutants, such as microcystin-LR [43], heavy metals [44] and industrial effluents [45]. It was reported that silica nanoparticles induced cardiac dysfunction of zebrafish embryo and inhibited the cardiac muscle contraction via affecting related genes, such as ATPase-related genes and regulatory gene tnnc1a for cardiac troponin C [46], and these genes were also altered in the liver of zebrafish exposed to the sampled Hun River water.…”

Section: Discussionsupporting

confidence: 74%

Transcriptomic Profiles in Zebrafish Liver Permit the Discrimination of Surface Water with Pollution Gradient and Different Discharges

Zhang

Liu

et al. 2018

IJERPH

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The present study aims to evaluate the potential of transcriptomic profiles in evaluating the impacts of complex mixtures of pollutants at environmentally relevant concentrations on aquatic vertebrates. The changes in gene expression were determined using microarray in the liver of male zebrafish (Danio rerio) exposed to surface water collected from selected locations on the Hun River, China. The numbers of differentially expressed genes (DEGs) in each treatment ranged from 728 to 3292, which were positively correlated with chemical oxygen demand (COD). Predominant transcriptomic responses included peroxisome proliferator-activated receptors (PPAR) signaling and steroid biosynthesis. Key pathways in immune system were also affected. Notably, two human diseases related pathways, insulin resistance and Salmonella infection were enriched. Clustering analysis and principle component analysis with DEGs differentiated the upstream and downstream site of Shenyang City, and the mainstream and the tributary sites near the junction. Comparison the gene expression profiles of zebrafish exposed to river surface water with those to individual chemicals found higher similarity of the river water with estradiol than several other organic pollutants and metals. Results suggested that the transcriptomic profiles of zebrafish is promising in differentiating surface water with pollution gradient and different discharges and in providing valuable information to support discharge management.

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Section: Discussionsupporting

confidence: 74%

Transcriptomic Profiles in Zebrafish Liver Permit the Discrimination of Surface Water with Pollution Gradient and Different Discharges

Zhang

Liu

et al. 2018

IJERPH

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“…The cell suspensions were centrifuged at 1,500 rpm for 5 minutes. In total, 5 mL cell lysate containing HNO 3 and H 2 O 2 (3:1) was added in cell pellets. Then, the silicon content in the lysis solution was detected using ICP-AES.…”

Section: Lactate Dehydrogenase Release Assaymentioning

confidence: 99%

“…Specifically, due to many advantages, 2 In recent years, the adverse effects of SiNPs on cardiovascular toxicity and atherosclerosis development have gained attention, and studies demonstrated a clear cardiovascular health risk associated with SiNPs exposure. 3,4 Vascular endothelia line the inner surface of blood vessels, and provide an essential structural and biological barrier to maintain vascular function and homeostasis. Endothelial dysfunction is now hypothesized to be a dominant mechanism in the development of cardiovascular diseases, including atherosclerosis and ischemic heart disease.…”

Section: Introductionmentioning

confidence: 99%

Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling

Guo¹,

Yang²,

Li³

et al. 2016

IJN

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192

111

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Environmental exposure to silica nanoparticles (SiNPs) is inevitable due to their widespread application in industrial, commercial, and biomedical fields. In recent years, most investigators focus on the evaluation of cardiovascular effects of SiNPs in vivo and in vitro. Endothelial injury and dysfunction is now hypothesized to be a dominant mechanism in the development of cardiovascular diseases. This study aimed to explore interaction of SiNPs with endothelial cells, and extensively investigate the exact effects of reactive oxygen species (ROS) on the signaling molecules and cytotoxicity involved in SiNPs-induced endothelial injury. Significant induction of cytotoxicity as well as oxidative stress, apoptosis, and autophagy was observed in human umbilical vein endothelial cells following the SiNPs exposure ( P <0.05). The oxidative stress was induced by ROS generation, leading to redox imbalance and lipid peroxidation. SiNPs induced mitochondrial dysfunction, characterized by membrane potential collapse, and elevated Bax and declined bcl-2 expression, ultimately leading to apoptosis, and also increased number of autophagosomes and autophagy marker proteins, such as LC3 and p62. Phosphorylated ERK, PI3K, Akt, and mTOR were significantly decreased, but phosphorylated JNK and p38 MAPK were increased in SiNPs-exposed endothelial cells. In contrast, all of these stimulation phenomena were effectively inhibited by N -acetylcysteine. The N -acetylcysteine supplement attenuated SiNPs-induced endothelial toxicity through inhibition of apoptosis and autophagy via MAPK/Bcl-2 and PI3K/Akt/mTOR signaling, as well as suppression of intracellular ROS property via activating antioxidant enzyme and Nrf2 signaling. In summary, the results demonstrated that SiNPs triggered autophagy and apoptosis via ROS-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling in endothelial cells, and subsequently disturbed the endothelial homeostasis and impaired endothelium. Our findings may provide experimental evidence and explanation for cardiovascular diseases triggered by SiNPs. Furthermore, results hint that the application of antioxidant may provide a novel way for safer use of nanomaterials.

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“…Usually, there was no or minimal damage to kidney when SiNPs were administered in vivo. 40,49,51 It had been reported that SiNPs induced cardiotoxicity to zebrafish embryo because these particles inhibited angiogenesis and disturbed heart formation and development; 52 neutrophil-mediated cardiac inflammation 53 was assumed to be the cause. However, no definite cardiac injury was noted in the studies 40,49,51 of mature mice.…”

mentioning

confidence: 99%

In vivo toxicologic study of larger silica nanoparticles in mice

Chan¹,

Liu²,

Chiau³

et al. 2017

IJN

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Silica nanoparticles (SiNPs) are being studied and used for medical purposes. As nanotechnology grows rapidly, its biosafety and toxicity have frequently raised concerns. However, diverse results have been reported about the safety of SiNPs; several studies reported that smaller particles might exhibit toxic effects to some cell lines, and larger particles of 100 nm were reported to be genotoxic to the cocultured cells. Here, we investigated the in vivo toxicity of SiNPs of 150 nm in various dosages via intravenous administration in mice. The mice were observed for 14 days before blood examination and histopathological assay. All the mice survived and behaved normally after the administration of nanoparticles. No significant weight change was noted. Blood examinations showed no definite systemic dysfunction of organ systems. Histopathological studies of vital organs confirmed no SiNP-related adverse effects. We concluded that 150 nm SiNPs were biocompatible and safe for in vivo use in mice.

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Low-dose exposure of silica nanoparticles induces cardiac dysfunction via neutrophil-mediated inflammation and cardiac contraction in zebrafish embryos

Cited by 124 publications

References 45 publications

Transcriptomic Profiles in Zebrafish Liver Permit the Discrimination of Surface Water with Pollution Gradient and Different Discharges

Transcriptomic Profiles in Zebrafish Liver Permit the Discrimination of Surface Water with Pollution Gradient and Different Discharges

Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling

In vivo toxicologic study of larger silica nanoparticles in mice

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