Search

Silica nanoparticles found in sugarcane ash have been postulated to be a toxicant contributing to chronic kidney disease (CKD) of unknown etiology. However, although the administration of manufactured silica nanoparticles is known to cause chronic tubulointerstitial disease in rats, the effect of administering sugarcane ash on kidney pathology remains unknown. Here, we investigated whether sugarcane ash can induce CKD in rats. Sugarcane ash was administered for 13 wk into the nares of rats (5 mg/day for 5 days/wk), and blood, urine, and kidney tissues were collected at 13 wk (at the end of ash administration) and in a separate group of rats at 24 wk (11 wk after ash administration was stopped). Kidney histology was evaluated, and inflammation and fibrosis (collagen deposition) were measured. Sugarcane ash exposure led to the accumulation of silica in the kidneys, lungs, liver, and spleen of rats. Mild proteinuria developed, although renal function was largely maintained. However, biopsies showed focal glomeruli with segmental glomerulosclerosis as well as tubulointerstitial inflammation and fibrosis that tended to worsen even after the ash administration had been stopped. Staining for the lysosomal marker lysosomal associated membrane protein-1 showed decreased staining in ash-administered rats consistent with lysosomal activation. In conclusion, sugarcane ash containing silica nanoparticles can cause CKD in rats. [ABSTRACT FROM AUTHOR]

Silica nanoparticles (SiNPs) released during the burning of sugarcane have been postulated to have a role in chronic kidney disease of unknown etiology. We tested the hypothesis that pristine SiNPs of the size present in sugarcane might cause chronic kidney injury when administered through the lung in rats. We administered 200- or 300-nm amorphous SiNPs twice weekly (4 mg/dose), or vehicle by oropharyngeal aspiration for 13 wk to rats followed by euthanasia after an additional 13 wk (26 wk total). Tissues were evaluated for the presence of SiNPs and evidence of histological injury. Both sizes of SiNPs caused kidney damage, with early tubular injury and inflammation (at week 13) that continued to inflammation and chronic fibrosis at week 26 despite discontinuation of the SiNP administration. Both sizes of SiNPs caused local inflammation in the lung and kidney and were detected in the serum and urine at week 13, and the 200-nm particles were also localized to the kidney with no evidence of retention of the 300-nm particles. At week 26, there was some clearance of the 200-nm silica from the kidneys, and urinary levels of SiNPs were reduced but still significant in both 200- and 300 nm-exposed rats. In conclusion, inhaled SiNPs cause chronic kidney injury that progresses despite stopping the SiNP administration. These findings support the hypothesis that human exposure to amorphous silica nanoparticles found in burned sugarcane fields could have a participatory role in chronic kidney disease of unknown etiology. [ABSTRACT FROM AUTHOR]

Environmental crystalline silica exposure has been associated with formation of autoantibodies and development of systemic autoimmune disease, but the mechanisms leading to these events are unknown. Silica exposure in autoimmune-prone New Zealand mixed (NZM) mice results in a significant exacerbation of systemic autoimmunity as measured by increases in autoantibodies and glomerulonephritis. Previous studies have suggested that silica-induced apoptosis of alveolar macrophages (AM) contributes to the generation of the autoantibodies and disease. Rottlerin has been reported to inhibit apoptosis in many cell types, possibly through direct or indirect effects on PKC[delta]. In this study, rottlerin reduced silica-induced apoptosis in bone marrow-derived macrophages as measured by DNA fragmentation. In NZM mice, RNA and protein levels of PKC[delta] were significantly elevated in AM 14 wk after silica exposure. Therefore, rottlefin was used to reduce apoptosis of AM and evaluate the progress of silica-exacerbated systemic autoimmune disease. Fourteen weeks after silica exposure, NZM mice had increased levels of anti-histone autoantibodies, high proteinuria, and glomerulonephritis. However, silica-instilled mice that also received weekly instillations of rottlerin had significantly lower levels of proteinuria, anti-histone autoantibodies, complement C3, and IgG deposition within the kidney. Weekly instillations of rottlerin in silica-instilled NZM mice also inhibited the upregulation of PKC[delta] in AM. Together, these data demonstrate that in vivo treatment with rottlerin significantly decreased the exacerbation of autoimmunity by silica exposure. alveolar macrophage; apoptosis; protein kinase C[delta];

Pulmonary instillation of multiwalled carbon nanotubes (MWCNT) has the potential to promote cardiovascular derangements, but the mechanisms responsible are currently unclear. We hypothesized that exposure to MWCNT would result in increased epithelial barrier permeability by 24 h postexposure and initiate a signaling process involving IL-6/gp130 transsignaling in peripheral vascular tissue. To test this hypothesis we assessed the impact of 1 and 10 μg/cm(2) MWCNT on transepithelial electrical resistance (TEER) and expression of barrier proteins and cell activation in vitro using normal human bronchial epithelial primary cells. Parallel studies using male Sprague-Dawley rats instilled with 100 μg MWCNT measured bronchoalveolar lavage (BAL) differential cell counts, BAL fluid total protein, and lung water-to-tissue weight ratios 24 h postexposure and quantified serum concentrations of IL-6, soluble IL-6r, and soluble gp130. Aortic sections were examined immunohistochemically for gp130 expression, and gp130 mRNA/protein expression was evaluated in rat lung, heart, and aortic tissue homogenates. Our in vitro findings indicate that 10 μg/cm(2) MWCNT decreased the development of TEER and zonula occludens-1 expression relative to the vehicle. In rats MWCNT instillation increased BAL protein, lung water, and induced pulmonary eosinophilia. Serum concentrations of soluble gp130 decreased, aortic endothelial expression of gp130 increased, and expression of gp130 in the lung was downregulated in the MWCNT-exposed group. We propose that pulmonary exposure to MWCNT can manifest as a reduced epithelial barrier and activator of vascular gp130-associated transsignaling that may promote susceptibility to cardiovascular derangements., (Copyright © 2016 the American Physiological Society.)