Alaa Fehaid^{1, 2}, Mohamed F. Hamed³, Mamdouh M. Abouelmagd², Akiyoshi Taniguchi^{1, 4,}

Silver nanoparticles (AgNPs) are widely used because of their anti-bacterial and anti-inflammatory properties; however, the adverse health effects of these nanoparticles, especially to the lungs, have been less studied. We thus investigated the inflammatory response of polyvinylpyrrolidone (PVP)-coated AgNPs and silver nitrate (AgNO₃) after 24 h, 14 days and 28 days of single intratracheal instillation in rats. The bronchoalveolar lavage fluid (BALF) samples were collected and analyzed; a significant influx of neutrophils into the lung was found in both treated groups after 24 h with a presence of AgNPs in the alveolar macrophages after 24 h, 14 days and 28 days of instillation. Pro-inflammatory cytokines and enzymatic activities showed a significant increase after 24 h in both treated groups with a higher significance in the AgNO₃-treated group than the AgNPs-treated group. After 28 days, these increases were completely recovered in the AgNO₃-treated group but were still present in the AgNPs-treated group. The gross examination of lung tissues revealed a clear focal inflammation in the AgNPs-treated group after 28 days. More than 29% and 9% of the initial dose of AgNPs were recovered in lung tissues after 1 day and 28 days, respectively. Comparatively, the AgNO₃-treated group recovered only 16.5% and 1%, suggesting that the silver ions are easily absorbed into the circulation and distributed to different tissues more than the nanoparticles. Our results indicated that the PVP-AgNPs caused a subchronic pulmonary inflammation compared to the acute one induced by the ionic form, which can be recovered easily.

silver nanoparticles, pulmonary inflammation, silver distribution, toxicity