A water-soluble, organosilane-based coating blocked acute and sub-chronic respirable crystalline silica-induced lung toxicity and systemic inflammation in an animal model

Abstract

Inhalation of respirable crystalline silica can cause pulmonary fibrosis and inflammation. Silica particles have a highly reactive surface that generates cell-damaging reactive oxygen species when fractured. The objective was to evaluate lung toxicity after exposure to silica coated with and without a water-soluble, organosilane-based coating (SIVO160). Male Sprague-Dawley rats were intratracheally instilled with silica (1 mg/rat), silica coated with SIVO160, SIVO160 alone, or saline (vehicle control). At 3, 10, 45, and 90 d after exposure, bronchoalveolar lavage (BAL) and histopathology were performed to assess lung toxicity. Whole blood was collected to evaluate systemic inflammation by differentiating circulating white blood cells. Also, samples of uncoated and coated silica were analyzed [(1) RapiFlex MALDI-ToF/ToF mass spectrometry; (2) digestion in phagolysosomal simulant fluid (PSF) and serum ultrafiltrate (SUF)] to confirm the SIVO160 coating on the surface of the silica particles after incubation in biological media. At each time point, silica significantly increased BAL fluid lactate dehydrogenase (lung injury) and the number of recovered lung macrophages and neutrophils (lung inflammation). These silica-induced elevations in lung toxicity were completely blocked at each time point when silica was coated with SIVO160 before exposure. At 45 d after exposure to uncoated silica, circulating total white blood cells, neutrophils, and lymphocytes were significantly elevated in the blood compared to the other groups. Lung exposure to silica pretreated with SIVO160 did not cause a significant elevation in any of the peripheral blood cell types at any time point when compared to the saline and SIVO160 alone. As assessed by mass spectrometry, multiple unique spectral peaks were detected on the surface of the silica+SIVO160 particle samples after an overnight incubation in saline. The peaks were absent in the uncoated silica sample spectra, confirming the coating’s presence on the particles. The time it took for removal by digestion of the SIVO160 coating on the silica was reflected by a short-term delay after incubation in both PSF and SUF, suggesting protection could be conveyed to lung cells by the coating during phagocytosis and particle deposition on lung tissue structures. Organosilane materials may be used as a possible mitigation strategy to potentially protect large numbers of workers exposed to respirable crystalline silica in multiple industries is important.