Aerosolized Silver Nanoparticles in the Rat Lung and Pulmonary Responses over Time

Abstract

Silver nanoparticle (Ag NP) production methods are being developed and refined to produce more uniform Ag NPs through chemical reactions involving silver salt solutions, solvents, and capping agents to control particle formation. These chemical reactants are often present as contaminants and/or coatings on the Ag NPs, which could alter their interactions in vivo. To determine pulmonary effects of citrate-coated Ag NPs, Sprague-Dawley rats were exposed once nose-only to aerosolized Ag NPs (20 nm [C20] or 110 nm [C110] Ag NPs) for six hours. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained at 1, 7, 21, and 56 days post exposure for analyses. Inhalation of Ag NPs, versus citrate buffer control, produced significant inflammatory and cytotoxic responses that were measured in BALF cells and supernatant. At Day 7, total cells, protein, and lactate dehydrogenase were significantly elevated in BALF, and peak histopathology was noted after C20 or C110 exposure versus control. At Day 21, BALF PMNs and tissue inflammation was significantly greater after C20 versus C110 exposure. By Day 56, inflammation was resolved in Ag NP-exposed animals. Overall, results suggest delayed, short-lived inflammatory and cytotoxic effects following C20 or C110 inhalation and potential for greater responses following C20 exposure.

Pro-Inflammatory versus Immunomodulatory Effects of Silver Nanoparticles in the Lung: The Critical Role of Dose, Size and Surface Modification

“…The effects of the Ag-NPs size and coating on pulmonary inflammation have been extensively studied in different rodent models and strains, with different particle sizes and concentrations [ 10 , 31 , 32 , 33 , 34 , 35 ]. Little difference has been shown following instillations of Ag-NPs coated with citrate or PVP, although citrate appears to increase the short-term lung inflammatory infiltrate and to slightly influence the long-term lung burden of Ag-NPs.…”

Current state of knowledge on the health effects of engineered nanomaterials in workers: a systematic review of human studies and epidemiological investigations

“…Concerning animal investigations, toxicity in the lungs, including inflammatory reactions and histopathological alterations (149)(150)(151)(152)(153)(154)(155)(156)(157)(158) were reported to be responsible for pulmonary functionality alterations (155,159) or allergic responses (160): however, other investigations have failed to detect hematological effects, systemic alterations, and pulmonary function test changes after Ag-ENM exposure (161,162). Histopathological changes in the kidney and liver (bile duct hyperplasia and necrosis) were identified after inhalation exposures, such as extra-pulmonary effects (155,158,159).…”

Genetic determinants of susceptibility to silver nanoparticle‐induced acute lung inflammation in mice

“…AgNP studies in Sprague-Dawley (SD) rats provide additional evidence that size may also modify the timing of the inflammatory response and that size and coating affect the quantity and localization of AgNPs (17)(18)(19)(20). Furthermore, in C57BL/6 mice, size modified the dose response and timing of citrate-coated AgNP-induced lung inflammation, and surface coating and size altered AgNP effects on lung surfactant proteins and lung mechanics after instillation (10,21).…”

“…Additional strain differences included significant increases relative to control in total BALF protein and bronchial hyper-responsiveness in BN rats compared with SD rats after exposure to 20-nm citrate-and PVP-coated AgNPs. Thus, in vivo studies indicate that particle size, coating, and animal strain influence AgNP-induced lung inflammation and toxicity (10,12,(17)(18)(19)(20)(21).…”