Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after intratracheal instillation in rats

Nadine Haberl,Carsten Schleh,Wolfgang G Kreyling,Stephanie Hirn,Matthias Epple,Jörg Diendorf,Alexander Wenk,Blair D Johnston,Fritz Krombach

doi:10.3762/bjnano.4.105

Abstract

Silver nanoparticles (AgNP) are among the most promising nanomaterials, and their usage in medical applications and consumer products is growing rapidly. To evaluate possible adverse health effects, especially to the lungs, the current study focused on the cytotoxic and proinflammatory effects of AgNP after the intratracheal instillation in rats. Monodisperse, PVP-coated AgNP (70 nm) showing little agglomeration in aqueous suspension were instilled intratracheally. After 24 hours, the lungs were lavaged, and lactate dehydrogenase (LDH), total protein, and cytokine levels as well as total and differential cell counts were measured in the bronchoalveolar lavage fluid (BALF). Instillation of 50 µg PVP-AgNP did not result in elevated LDH, total protein, or cytokine levels in BALF compared to the control, whereas instillation of 250 µg PVP-AgNP caused a significant increase in LDH (1.9-fold) and total protein (1.3-fold) levels as well as in neutrophil numbers (60-fold) of BALF. Furthermore, while there was no change in BALF cytokine levels after the instillation of 50 µg PVP-AgNP, instillation of 250 µg PVP-AgNP resulted in significantly increased levels of seven out of eleven measured cytokines. These finding suggest that exposure to inhaled AgNP can induce moderate pulmonary toxicity, but only at rather high concentrations.

Highlights

Silver nanoparticles (AgNP) are among the most promising nanomaterials, and their usage in medical applications and consumer products is growing rapidly [1]
Direct pulmonary responses such as lactate dehydrogenase (LDH), protein, and cytokine levels in bronchoalveolar lavage fluid (BALF) were not assessed in these studies
We demonstrate that the intratracheal instillation of 250 μg, but not of 50 μg, of monodisperse PVP-coated 70 nm AgNP in rats caused cytotoxic and inflammatory responses of the lungs, as shown by elevated BALF LDH, protein, and cytokine levels as well as neutrophil numbers

Summary

Introduction

Silver nanoparticles (AgNP) are among the most promising nanomaterials, and their usage in medical applications and consumer products is growing rapidly [1]. With regard to the use in hygiene and health care spray products, AgNP had become present in everyday life In case of such aerosolized AgNP, the lungs with their large surface area are the first organs that come into contact with inhaled AgNP [8,9]. Nanoparticles are found to interact with the epithelial lining fluid including pulmonary surfactant, lung macrophages and epithelial cells [13,14,15]. Depending on their physico-chemical properties, a small portion of the inhaled nanomaterials may even be able to cross the air-blood-barrier (ABB), towards circulation, and accumulate in secondary organs [16,17]

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