Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague-Dawley rats
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Published version
Accepted version
Author(s)
Type
Journal Article
Abstract
Background
The 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 preinflammatory
state compared to Sprague-Dawley (SD) rats.
Methods
We 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.
Results
In both strains, there was an increase in neutrophils in bronchoalveolar lavage (BAL) fluid at
24 hours 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.
Conclusions
Presence 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.
The 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 preinflammatory
state compared to Sprague-Dawley (SD) rats.
Methods
We 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.
Results
In both strains, there was an increase in neutrophils in bronchoalveolar lavage (BAL) fluid at
24 hours 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.
Conclusions
Presence 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.
Date Issued
2016-07-19
Date Acceptance
2016-07-13
Citation
Respiratory Research, 2016, 17
ISSN
1465-993X
Publisher
BioMed Central
Journal / Book Title
Respiratory Research
Volume
17
Copyright Statement
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
License URL
Sponsor
Natural Environment Research Council (NERC)
National Institutes of Health
Grant Number
NE/H012893/1
H50669
Subjects
Inflammation
Inhalation
Lungs
Silver nanospheres
Respiratory System
1102 Cardiovascular Medicine And Haematology
1103 Clinical Sciences
Publication Status
Published
Article Number
85