Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague-Dawley rats. 2016

Joanna Seiffert, and Alison Buckley, and Bey Leo, and Nicholas G Martin, and Jie Zhu, and Ranran Dai, and Farhana Hussain, and Chang Guo, and James Warren, and Alan Hodgson, and Jicheng Gong, and Mary P Ryan, and Junfeng Jim Zhang, and Alexandra Porter, and Terry D Tetley, and Andrew Gow, and Rachel Smith, and Kian Fan Chung
Airways Disease, National Heart & Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK.

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 pre-inflammatory state compared to Sprague-Dawley (SD) rats. We determined the effect of AgNPs generated from a spark generator (mass concentration: 600-800 μg/mm(3); 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. In 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. 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.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D010743 Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Phosphatides,Phospholipid
D011014 Pneumonia Infection of the lung often accompanied by inflammation. Experimental Lung Inflammation,Lobar Pneumonia,Lung Inflammation,Pneumonia, Lobar,Pneumonitis,Pulmonary Inflammation,Experimental Lung Inflammations,Inflammation, Experimental Lung,Inflammation, Lung,Inflammation, Pulmonary,Inflammations, Lung,Inflammations, Pulmonary,Lobar Pneumonias,Lung Inflammation, Experimental,Lung Inflammations,Lung Inflammations, Experimental,Pneumonias,Pneumonias, Lobar,Pneumonitides,Pulmonary Inflammations
D011657 Pulmonary Eosinophilia A condition characterized by infiltration of the lung with EOSINOPHILS due to inflammation or other disease processes. Major eosinophilic lung diseases are the eosinophilic pneumonias caused by infections, allergens, or toxic agents. Eosinophilia, Pulmonary,Eosinophilic Pneumonia,Loeffler Syndrome,Pneumonia, Eosinophilic,Eosinophilias, Pulmonary,Pulmonary Eosinophilias,Simple Pulmonary Eosinophilia,Tropical Eosinophilic Pneumonia,Eosinophilic Pneumonia, Tropical,Eosinophilic Pneumonias,Eosinophilic Pneumonias, Tropical,Pneumonias, Eosinophilic,Pulmonary Eosinophilia, Simple,Simple Pulmonary Eosinophilias,Syndrome, Loeffler,Tropical Eosinophilic Pneumonias
D011914 Rats, Inbred BN An inbred strain of rat that is widely used in a variety of research areas such as the study of ASTHMA; CARCINOGENESIS; AGING; and LEUKEMIA. Rats, Inbred Brown Norway,Rats, BN,BN Rat,BN Rat, Inbred,BN Rats,BN Rats, Inbred,Inbred BN Rat,Inbred BN Rats,Rat, BN,Rat, Inbred BN
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012834 Silver An element with the atomic symbol Ag, atomic number 47, and atomic weight 107.87. It is a soft metal that is used medically in surgical instruments, dental prostheses, and alloys. Long-continued use of silver salts can lead to a form of poisoning known as ARGYRIA.

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