Inhalation exposure to ethylene induces eosinophilic rhinitis and nasal epithelial remodeling in Fischer 344 rats

Brandenberger, Christina; Hotchkiss, Jon A.; Krieger, Shannon M.; Pottenger, Lynn H.; Harkema, Jack R.

doi:10.1016/j.cbi.2015.09.001

Cited by 3 publications

(5 citation statements)

References 24 publications

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“…This is also consistent with the finding of Brandenberger et al that 20 consecutive weekday exposures to 10,000 ppm ethylene did not cause an increase in serum levels of immunoglobulins, IgG1, IgG2a, and IgE. 8…”

Section: Discussionsupporting

confidence: 93%

“…Airway mucosa lining the NPM was microdissected and processed for quantitative PCR as previously described in detail. 8,19…”

Section: Resultsmentioning

confidence: 99%

“…More recently, we have reported that repeated inhalation exposures of F344/DuCrl rats to ethylene (6 h/d, 5 d/wk for up to 4 weeks; continuous exposure) caused a dose- and time-dependent mucous cell hyperplasia/hypertrophy (MCH) in nasal respiratory epithelium along with a focal eosinophilic rhinitis, both of which were associated with type 2 immunity. 8 There was a significant increase in MCH after 5 days of exposure to 10,000 ppm ethylene and after 20 days of exposure to 10 ppm ethylene. Ethylene-induced MCH was, however, reversible after cessation of exposure.…”

Section: Introductionmentioning

confidence: 89%

“…For quantification of AB/PAS-positive, intraepithelial mucosubstances, digital images of the respiratory nasal epthelium lining the proximal mid-septum (MS) in both nasal passages (T1 section) and the distal nasopharyngeal meatus (NPM; T4 section) were evaluated via morphometric methods using the newCAST software (VisioPharm) that has been previously described in detail. 8 , 19 For quantification of AB/PAS-positive, intraepithelial mucosubstances, the entire respiratory epithelium lining the MS in the T1 section and the NPM in the T4 section were selected and captured at ×400 magnification (one tissue section per animal). A point intercept grid was placed over the sampled images to estimate density of mucosubstances per basal lamina.…”

Section: Methodsmentioning

confidence: 99%

“…Airway mucosa lining the NPM was microdissected and processed for quantitative PCR as previously described in detail. 8,19 An array with different genes associated with type 1 and type 2 immunity/inflammation and airway mucus production/ secretion was performed on pooled group samples. Genes that showed a higher than 1.5-fold increase or decrease relative to FA controls were further analyzed on individual samples and statistically evaluated (Table 1).…”

Section: Rats Episodically Exposed To Ethylenementioning

confidence: 99%

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Pathogenesis and Persistence of Increased Epithelial Mucosubstances in the Nasal Airways of Rats and Mice Episodically Exposed to Ethylene

et al. 2020

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Rats repeatedly exposed to high airborne concentrations of ethylene develop eosinophilic rhinitis and mucous cell hyperplasia/hypertrophy (MCH) in nasal respiratory epithelium. Mechanisms underlying these lesions are not well understood to inform occupational exposure guidelines. In this study, we determined (1) the nasal histopathology in rats episodically exposed to ethylene, (2) the ethylene-induced nasal histopathology in similarly exposed mice, and (3) how innate lymphoid cells (ILCs) play a role in ethylene-induced MCH. Animals were exposed to 0 or 10,000 ppm ethylene, 6 h/d, 5 d/wk, for 2 weeks and sacrificed 1 day or 2 weeks postexposure. Others received three 2-week exposure blocks separated by 2-week intervals of no exposure. Episodic exposure was chosen to aid in distinguishing irritant from immune responses. Mucous cell hyperplasia/hypertrophy was induced by ethylene in both species. Rats developed a mild, but transient, eosinophilic rhinitis. Mucous cell hyperplasia/hypertrophy was transient in mice, but persistent in rats. Increases in epithelial mucosubstances after 2 weeks of exposure were only present in ILC-sufficient mice, but not in ILC-deficient mice suggesting that ILCs play a role in MCH and overexpression of genes associated with mucus production/secretion. These findings in animals suggest that inhaled ethylene does not act as a sensitizing agent and will not induce allergen-like nasal airway disease.

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Section: Discussionsupporting

confidence: 93%

“…Airway mucosa lining the NPM was microdissected and processed for quantitative PCR as previously described in detail. 8,19…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Rats Episodically Exposed To Ethylenementioning

confidence: 99%

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Pathogenesis and Persistence of Increased Epithelial Mucosubstances in the Nasal Airways of Rats and Mice Episodically Exposed to Ethylene

et al. 2020

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Evaluation of the toxicity of ZnO nanoparticles obtained by a chemical route on the nasal respiratory epithelium of the biomodel Mus musculus

Mosquera-Murillo,

Castañeda-Manquillo,

Ángel-Camilo

et al. 2023

J Nanopart Res

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Zinc oxide nanoparticles (ZnO-NPs) have antimicrobial and a number of other properties, rendering apt their use in biomedicine, environmental remediation, agriculture, and other fields. Given the potential use of these nanoparticles (NPs) in these areas, it is necessary to determine their toxic effects on biological systems. This work therefore analyzed the histological changes in the respiratory nasal epithelium of Mus musculus biomodels exposed to atmospheres containing ZnO-NPs at different concentrations (6, 15, and 40 mg/m3). The NPs were synthesized using the Pechini polymeric complex method and characterized using techniques such as IR and Raman spectroscopies, X-ray diffraction (XRD), transmission (TEM), and scanning electron microscopy (SEM). The ZnO-NPs obtained had a wurtzite-type structure, with spheroidal morphology and a particle size of ~ 50 nm, and the Raman spectrum showed the presence of defects in its structure. The results of the treatments to which the biomodels were subjected showed that the inhalation of ZnO-NPs caused significant morphological changes in their nasal epithelium (squamous metaplasia and vascular congestion) and an acute inflammatory response when exposed to high concentrations of NPs (40 and 15 mg/m3). Graphical Abstract

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A physiologically based toxicokinetic model for inhaled ethylene and ethylene oxide in mouse, rat, and human

Filser

Klein

2018

Toxicology Letters

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Ethylene (ET) is the largest volume organic chemical. Mammals metabolize the olefin to ethylene oxide (EO), another important industrial chemical. The epoxide alkylates macromolecules and has mutagenic and carcinogenic properties. In order to estimate the EO burden in mice, rats, and humans resulting from inhalation exposure to gaseous ET or EO, a physiological toxicokinetic model was developed. It consists of the compartments lung, richly perfused tissues, kidneys, muscle, fat, arterial blood, venous blood, and liver containing the sub-compartment endoplasmic reticulum. Modeled ET metabolism is mediated by hepatic cytochrome P450 2E1, EO metabolism by hepatic microsomal epoxide hydrolase or cytosolic glutathione S-transferase in various tissues. EO is also spontaneously hydrolyzed or conjugated with glutathione. The model was validated on experimental data collected in mice, rats, and humans. Modeled were uptake by inhalation, wash-in-wash-out effect in the upper respiratory airways, distribution into tissues and organs, elimination via exhalation and metabolism, and formation of 2-hydroxyethyl adducts with hemoglobin and DNA. Simulated concentration-time courses of ET or EO in inhaled (gas uptake studies) or exhaled air, and of EO in blood during exposures to ET or EO agreed excellently with measured data. Predicted levels of adducts with DNA and hemoglobin, induced by ET or EO, agreed with reported levels. Exposures to 10000 ppm ET were predicted to induce the same adduct levels as EO exposures to 3.95 (mice), 5.67 (rats), or 0.313 ppm (humans). The model is concluded to be applicable for assessing health risks from inhalation exposure to ET or EO.

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Inhalation exposure to ethylene induces eosinophilic rhinitis and nasal epithelial remodeling in Fischer 344 rats

Cited by 3 publications

References 24 publications

Pathogenesis and Persistence of Increased Epithelial Mucosubstances in the Nasal Airways of Rats and Mice Episodically Exposed to Ethylene

Pathogenesis and Persistence of Increased Epithelial Mucosubstances in the Nasal Airways of Rats and Mice Episodically Exposed to Ethylene

Evaluation of the toxicity of ZnO nanoparticles obtained by a chemical route on the nasal respiratory epithelium of the biomodel Mus musculus

A physiologically based toxicokinetic model for inhaled ethylene and ethylene oxide in mouse, rat, and human

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