Amorphous silica nanoparticle-induced pulmonary inflammatory response depends on particle size and is sex-specific in rats

Han, Hyoung-Yun; Cho, Jae-Woo; Seong, Eunsol; Park, Eun-Jun; Lee, Gwang Hee; Kim, Dong Wan; Yang, Young-Su; Oh, Jung Hwa; Yoon, Seokjoo; Lee, Tae Geol; Kim, Tae Won

doi:10.1016/j.taap.2020.114890

Cited by 15 publications

(8 citation statements)

References 45 publications

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“…As described for micrometric crystalline and amorphous silica, in vivo experimental studies with nanometric amorphous silica confirm that it also induces a significant increase in total BALF cells [ 38 , 43 , 56 , 61 , 62 ]. Examination of the different cell types in BALF reveals a significant increase in neutrophil [ 38 , 43 , 56 , 57 , 62 ], eosinophil [ 54 ], and macrophage and lymphocyte [ 56 ] numbers. The neutrophil influx is size dependent (higher upon exposure to smaller particles) [ 43 , 54 , 55 ].…”

Section: Biological Effects Of Micro- and Nanometric Crystalline Or A...mentioning

confidence: 81%

“…In “nose-only” inhalation studies, rats were exposed to ambient doses between 2.6 and 27 mg/m 3 , for 4 or 6 h per day, with observation timepoints covering the full range [ 26 , 43 ]. Intratracheal instillations in rodents were performed mainly as a single 0.02 to 160 mg/kg dose, and observation timepoints once again covered the full range (acute, subacute, subchronic, or chronic) [ 38 , 43 , 53 , 54 , 55 , 56 , 57 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ].…”

Section: Experimental Designsmentioning

confidence: 99%

“…Indeed, after exposure to nanometric amorphous silica, high expression of proinflammatory proteins or mRNA molecules is detected in human and rodent pulmonary epithelial cell lines. Thus, reports indicate significantly increased protein expression for a number of proinflammatory markers such as TNF-α [ 62 , 88 ], CXCL1 [ 62 ], IL-6 [ 62 , 88 , 89 ], IL-8 [ 88 , 89 ], MIP-1α [ 88 ], MIP-1β [ 88 ] and MIP-2 [ 90 ], and increased mRNA expression for IL-6 and IL-8 [ 87 , 91 ].…”

Section: Biological Effects Of Micro- and Nanometric Crystalline Or A...mentioning

confidence: 99%

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Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review

et al. 2022

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Silicon dioxide (SiO2) is a mineral compound present in the Earth’s crust in two mineral forms: crystalline and amorphous. Based on epidemiological and/or biological evidence, the pulmonary effects of crystalline silica are considered well understood, with the development of silicosis, emphysema, chronic bronchitis, or chronic obstructive pulmonary disease. The structure and capacity to trigger oxidative stress are recognized as relevant determinants in crystalline silica’s toxicity. In contrast, natural amorphous silica was long considered nontoxic, and was often used as a negative control in experimental studies. However, as manufactured amorphous silica nanoparticles (or nanosilica or SiNP) are becoming widely used in industrial applications, these paradigms must now be reconsidered at the nanoscale (<100 nm). Indeed, recent experimental studies appear to point towards significant toxicity of manufactured amorphous silica nanoparticles similar to that of micrometric crystalline silica. In this article, we present an extensive review of the nontumoral pulmonary effects of silica based on in vitro and in vivo experimental studies. The findings of this review are presented both for micro- and nanoscale particles, but also based on the crystalline structure of the silica particles.

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Section: Biological Effects Of Micro- and Nanometric Crystalline Or A...mentioning

confidence: 81%

Section: Experimental Designsmentioning

confidence: 99%

Section: Biological Effects Of Micro- and Nanometric Crystalline Or A...mentioning

confidence: 99%

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Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review

et al. 2022

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“…For example, PEG-coated gold NPs show different toxic effects in male and female mice, producing more severe kidney damage in females, but higher liver toxicity in males 12 . In another study, amorphous silica NPs triggered more-severe inflammation and lung tissue damage in female rats compared to male rats 13 .…”

Section: Introductionmentioning

confidence: 93%

Sex as an important factor in nanomedicine

et al. 2021

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Nanomedicine has demonstrated substantial potential to improve the quality and efficacy of healthcare systems. Although the promise of nanomedicine to transform conventional medicine is evident, significant numbers of therapeutic nanomedicine products have failed in clinical trials. Most studies in nanomedicine have overlooked several important factors, including the significance of sex differences at various physiological levels. This report attempts to highlight the importance of sex in nanomedicine at cellular and molecular level. A more thorough consideration of sex physiology, among other critical variations (e.g., health status of individuals), would enable researchers to design and develop safer and more-efficient sex-specific diagnostic and therapeutic nanomedicine products.

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“…Amorphous silica nanoparticles (ASNP) have been the subject of an increasing number of toxicological studies given that they are present in a variety of common consumer products and widely used for biomedical applications and as a food additive [1][2][3][4][5]. Although synthetic amorphous silica has been considered safe for many decades, recent investigations have highlighted the pro-inflammatory effects of ASNPs [6][7][8][9][10][11][12][13] as well as their hazard potential and accumulation in several organs [14,15]. In the growing debate about the biological effects of engineered nanomaterials (ENM), an issue of interest consists of the possibility that they interfere with the response of immune cells to other agents, potentially affecting inflammation pathways [16].…”

Section: Introductionmentioning

confidence: 99%

The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles

et al. 2022

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Amorphous silica nanoparticles (ASNP) are present in a variety of products and their biological effects are actively investigated. Although several studies have documented pro-inflammatory effects of ASNP, the possibility that they also modify the response of innate immunity cells to natural activators has not been thoroughly investigated. Here, we study the effects of pyrogenic ASNP on the LPS-dependent activation of human macrophages differentiated from peripheral blood monocytes. In macrophages, 24 h of pre-exposure to non-cytotoxic doses of ASNP markedly inhibited the LPS-dependent induction of pro-inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10). The inhibitory effect was associated with the suppression of NFκB activation and the increased intracellular sequestration of the TLR4 receptor. The late induction of glutamine synthetase (GS) by LPS was also prevented by pre-exposure to ASNP, while GS silencing did not interfere with cytokine secretion. It is concluded that (i) macrophages exposed to ASNP are less sensitive to LPS-dependent activation and (ii) GS induction by LPS is likely secondary to the stimulation of cytokine secretion. The observed interference with LPS effects may point to a dampening of the acute inflammatory response after exposure to ASNP in humans.

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Amorphous silica nanoparticle-induced pulmonary inflammatory response depends on particle size and is sex-specific in rats

Cited by 15 publications

References 45 publications

Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review

Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review

Sex as an important factor in nanomedicine

The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles

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