The purpose of this work was to investigate the cardiovascular toxicity of different sizes and different dosages of silica nanoparticles in Wistar rats. The three silica nanoparticles (30, 60, and 90 nm) and one fine silica particles (600 nm) at three doses of 2, 5, and 10 (mg/Kg bw) were used in the present experiment. After intratracheal instillation for a total of 16 times, concentration of Si in hearts and serum was measured by inductively coupled plasma optical emission spectrometer. The hematology parameters were analyzed by an automated hematology analyzer, and the inflammatory reaction, oxidative stress, endothelial dysfunction, and the myocardial enzymes in serum were measured by kits. Our results showed intratracheal-instilled silica nanoparticles could pass through the alveolar-capillary barrier into systemic circulation. Concentration of Si in the heart and serum depended on the particles size and dosage. The levels of reactive oxygen species (ROS) at 5, 10 mg/Kg bw of the three silica nanoparticles were higher than the fine silica particles. Blood levels of inflammation-related high-sensitivity C-reactive protein and cytokines such as interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha were increased after exposure to three silica nanoparticles at 10 mg/Kg bw. Moreover, the levels of IL-1β and IL-6 at 10 mg/Kg bw of silica nanoparticles (30 nm) were higher than the fine silica particles. Significant decrease in superoxide dismutase, glutathione peroxidase and significant increase in malondialdehyde were observed at 10 mg/Kg bw of the three silica nanoparticles. A significant decrease in nitric oxide (NO) production was induced which coincided with the reduction of nitric oxide synthase (NOS) activity and the excessive generation of ROS in rats. The levels of intercellular adhesion molecule-l and vascular cell adhesion molecule-l elevated significantly after exposure to three silica nanoparticles at 10 mg/Kg bw, which are considered as early steps of endothelial dysfunction. We conclude that cardiovascular toxicity of silica nanoparticles could be related to the particles size and dosage. Oxidative stress could be involved in inflammatory reaction and endothelial dysfunction, all of which could aggravate cardiovascular toxicology. In addition, endothelial NO/NOS system disorder caused by nanoparticles could be one of the mechanisms for endothelial dysfunction.

BackgroundSilicosis has been topping the list of high-incidence occupational diseases in developing countries and cannot be completely cured. Recent advances in stem cell research have made possible the treatment of various diseases including lung fibrosis. The application of stem cell therapy in occupational diseases, in particular the use of adipose-derived mesenchymal stem cells (AD-MSCs) in treatment of silicosis, has not yet been reported. The aim of the study is to explore the intervening effect of silica-induced lung fibrosis in rats.MethodsIn this study, we investigated the anti-pulmonary fibrosis effects of the transplantation of AD-MSCs in rats in which lung fibrosis was induced by oral tracheal intubation with silica suspension. Twenty rats were divided into four groups: control group (n = 5), exposure group (n = 5), vehicle group (n = 5) and treatment group (n = 5). AD-MSCs were given to rats after exposure to silica for 24 h. Twenty-eight days after AD-MSC transplantation, we examined the organ coefficient, inflammatory cytokines, apoptosis, pathological and fibrotic changes in lung tissue.ResultsResults showed that exposure to silica for 28 days induced an increase of the lung coefficient with significant pulmonary fibrosis. Treatment with AD-MSC transplantation led to a remissive effect on pulmonary fibrosis. We found that after AD-MSC transplantation the inflammatory response decreased and Caspase-3 protein expression significantly decreased with a significant increase of the Bcl-2/Bax ratio.ConclusionsAnti-inflammatory and anti-apoptosis of AD-MSCs may play important roles in their anti-pulmonary fibrosis effect. Our data suggest that transplantation of AD-MSCs holds promise for potential interference in the formation of silicosis through regulating inflammatory and apoptotic processes.

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