Pulmonary Inflammation in Brown Norway Rats: Possible Association of Environmental Particles in the Animal Room Environment

Noritake, Shinobu; Ogawa, Koji; Suzuki, Go; Ozawa, K; Ikeda, Takuya

doi:10.1538/expanim.56.319

Cited by 12 publications

(5 citation statements)

References 21 publications

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“…The response to AgNPs by direct inhalation into lungs, which would be the main route of exposure if humans were exposed to AgNPs from consumer products, remains unclear particularly in the potential differences in the response between the 2 rat strains. The BN rat is known to readily develop features of allergic asthma, namely lung eosinophilia and bronchial hyperresponsiveness (BHR) following sensitisation and exposure to allergens and possess features of chronic lung inflammation in contrast to the SD rat [ 17 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague–Dawley rats

et al. 2016

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BackgroundThe increasing use of silver nanoparticles (AgNPs) in consumer products is concerning. We examined the potential toxic effects when inhaled in Brown-Norway (BN) rats with a pre-inflammatory state compared to Sprague–Dawley (SD) rats.MethodsWe determined the effect of AgNPs generated from a spark generator (mass concentration: 600–800 μg/mm3; mean diameter: 13–16 nm; total lung doses: 8 [Low] and 26–28 [High] μg) inhaled by the nasal route in both rat strains. Rats were sacrificed at day 1 and day 7 after exposure and measurement of lung function.ResultsIn both strains, there was an increase in neutrophils in bronchoalveolar lavage (BAL) fluid at 24 h at the high dose, with concomitant eosinophilia in BN rats. While BAL inflammatory cells were mostly normalised by Day 7, lung inflammation scores remained increased although not the tissue eosinophil scores. Total protein levels were elevated at both lung doses in both strains. There was an increase in BAL IL-1β, KC, IL-17, CCL2 and CCL3 levels in both strains at Day 1, mostly at high dose. Phospholipid levels were increased at the high dose in SD rats at Day 1 and 7, while in BN rats, this was only seen at Day 1; surfactant protein D levels decreased at day 7 at the high dose in SD rats, but was increased at Day 1 at the low dose in BN rats. There was a transient increase in central airway resistance and in tissue elastance in BN rats at Day 1 but not in SD rats. Positive silver-staining was seen particularly in lung tissue macrophages in a dose and time-dependent response in both strains, maximal by day 7. Lung silver levels were relatively higher in BN rat and present at day 7 in both strains.ConclusionsPresence of cellular inflammation and increasing silver-positive macrophages in lungs at day 7, associated with significant levels of lung silver indicate that lung toxicity is persistent even with the absence of airway luminal inflammation at that time-point. The higher levels and persistence of lung silver in BN rats may be due to the pre-existing inflammatory state of the lungs.

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Section: Introductionmentioning

confidence: 99%

Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague–Dawley rats

et al. 2016

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“…Since basic IgE levels were still high one may speculate that pre-sensitization of the animals could have occurred, in which case an increase due to OVA sensitization would hardly be visible. Presensitization is conceivable, since in Brown-Norway rats pulmonary inflammation has been observed under normal animal room environment due to ambient particles (0.3 -1 µm in diameter) and the number of those particles correlated strongly with the number of eosinophils in the bronchoalveolar lavage fluid (133). However, in the present study lung tissue was reserved for PCLS preparation, which excluded the determination of eosinophils.…”

Section: Sensitization Schemementioning

confidence: 64%

Electric field stimulation of precision-cut lung slices

Schlepütz

Uhlig

Martin

2011

Journal of Applied Physiology

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The precision-cut lung slice (PCLS) technique is widely used to examine airway responses in different species. We developed a method to study nerve-dependent bronchoconstriction by the application of electric field stimulation (EFS) to PCLS. PCLS prepared from Wistar rats were placed between two platinum electrodes to apply serial rectangular impulses (5-100 Hz), and bronchoconstriction was studied by videomicroscopy. The extent of airway contractions increased with higher frequencies. Stable repeated airway contractions were obtained at a frequency of 50 Hz, a width of 1 ms, and an output of 200 mA for 2.5 s each minute. Larger airways showed stronger responses. The EFS-triggered contractions were increased by the acetylcholine esterase inhibitor neostigmine (10 μM) and reversed by the muscarinic antagonist atropine (10 μM), whereas the thromboxane protanoid receptor antagonist SQ29548 (10 μM) had no effect. Magnesium ions (10 mM) antagonized airway contractions induced by EFS, but not by methacholine, indicating that nerve endings remain intact in PCLS. Our data further show that the electrically evoked airway contractions in PCLS are mediated by cholinergic nerves, independent of thromboxane and more prominent in larger airways. Taken together these findings show that nerve endings remain intact in PCLS, and they suggest that the present method is useful to study neurogenic responses in airways of different size.

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“…A more sophisticated approach could therefore comprise a titration of the adjuvants to Since basic IgE levels were still high one may speculate that pre-sensitization of the animals could have occurred, in which case an increase due to OVA sensitization would hardly be visible. Presensitization is conceivable, since in Brown-Norway rats pulmonary inflammation has been observed under normal animal room environment due to ambient particles (0.3 -1 µm in diameter) and the number of those particles correlated strongly with the number of eosinophils in the bronchoalveolar lavage fluid (133). However, in the present study lung tissue was reserved for PCLS preparation, which excluded the determination of eosinophils.…”

Section: Sensitization Schemementioning

confidence: 64%