Experimental study on the effect of Si and P ion content in SiO2 exposure environment on the degree of pulmonary fibrosis.

BACKGROUND: Silicosis is a public health issue in developing countries for long and cannot be completely cured. OBJECTIVE: To study the changes of ion content with TNF-α and TGF-ß expression in alveolar lavage fluid (BALF) at different time points in rats exposed to silica and to investigate their correlation with pulmonary fibrosis. METHODS: 42 rats were randomly divided into control group (n = 12) and exposure group (n = 30). Tissues of right lower lungs were collected and fixed for further Hematoxylin-eosin (HE) and Masson staining. We collected the BALF to examine the inflammatory cytokines of TNF-α and TGF-ß and measured the ion contents in BALF. RESULTS: The increase of TNF-α level was earlier than TGF-ß. The content of silica in BALF was significantly increased after exposure and reached the maximum at 7th day, similar to the curve of cytokine TGF-ß level. However, phosphorus ions increased quickly after gradual decline of silicon ion and roughly proportional to the curve of degree of fibrosis. CONCLUSIONS: Crystalline silica exposure can cause changes in TGF-ß and TNF-α in BALF and accompanied with fibrosis and ions content variation. The abnormal expression of phosphorus ion may have significance in the occurrence and development of silicosis.

Alpha-lipoic acid attenuates silica-induced pulmonary fibrosis by improving mitochondrial function via AMPK/PGC1α pathway activation in C57BL/6J mice.

Silicosis is characterized by pulmonary interstitial fibrosis that arises as a result of chronic exposure to silica. The few available treatments only delay its progression. As α-lipoic acid (ALA) has been shown to have various beneficial effects, including mitoprotective, antioxidant, and anti-inflammatory effects, we hypothesized that it may exhibit therapeutic effects in pulmonary fibrosis. Therefore, in the present study, we used a murine model of silicosis to investigate whether supplementation with exogenous ALA could attenuate silica-induced pulmonary fibrosis by improving mitochondrial function. ALA was administered to the model mice via continuous intragastric administration for 28 days, and then the antioxidant and mitoprotective effects of ALA were evaluated. The results showed that ALA decreased the production of reactive oxygen species, protected mitochondria from silica-induced dysfunction, and inhibited extracellular matrix deposition. ALA also decreased hyperglycemia and hyperlipidemia. Activation of the mitochondrial AMPK/PGC1α pathway might be responsible for these ALA-mediated anti-fibrotic effects. Exogenous ALA blocked oxidative stress by activating NRF2. Taken together, these findings demonstrate that exogenous ALA effectively prevents the progression of silicosis in a murine model, likely by stimulating mitochondrial biogenesis and endogenous antioxidant responses. Therefore, ALA can potentially delay the progression of silica-induced pulmonary fibrosis.

Earthworm extract attenuates silica-induced pulmonary fibrosis through Nrf2-dependent mechanisms.

Silicosis is an occupational pulmonary fibrosis caused by inhalation of silica (SiO2) and there are no ideal drugs to treat this disease. Earthworm extract (EE), a natural nutrient, has been reported to have anti-inflammatory, antioxidant, and anti-apoptosis effects. The purpose of the current study was to test the protective effects of EE against SiO2-induced pulmonary fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. We found that treatment with EE significantly reduced lung inflammation and fibrosis and improved lung structure and function in SiO2-instilled mice. Further mechanistic investigations revealed that EE administration markedly inhibited SiO2-induced oxidative stress, mitochondrial apoptotic pathway, and epithelial-mesenchymal transition in HBE and A549 cells. Furthermore, we demonstrate that Nrf2 activation partly mediates the interventional effects of EE against SiO2-induced pulmonary fibrosis. Our study has identified EE to be a potential anti-oxidative, anti-inflammatory, and anti-fibrotic drug for silicosis.

[Effects of Qili Qiangxin capsules on NT-proBNP level and cardiac function in silicosis patients].

OBJECTIVE: To investigate the effects of Qili Qiangxin capsules on the amino-terminal pro-brain natriuretic peptide (NT-proBNP) level and cardiac function in patients with silicosis. METHODS: Hospitalized silicosis patients with heart failure were divided into treatment group (41 cases) and control group (30 cases) according to their own will. Both groups received comprehensive symptomatic treatment; in addition, the treatment group received Qili Qiangxin capsules. The treatment lasted 6 months. The observed items included NT-proBNP level, 6-minute walk test, ultrasonic cardiogram, and NYHA classification before and after treatment. RESULTS: According to NYHA classification, the response rate was 29.27%in the treatment group and 10.00%in the control group; there was a significant difference between the two groups (P < 0.05). The average walk distance in the treatment group was increased from 150.96±73.12 m before treatment to 169.32±77.04 m after treatment, and the improvement was statistically significant (P < 0.05). The average NT-proBNP level in the treatment group was reduced from 1154.44 ± 480.79 ng/L before treatment to 494.49 ± 342.61 ng/L after treatment, and the reduction was statistically significant (P < 0.01). Left ventricular ejection fraction was significantly improved in the treatment group (P < 0.05). CONCLUSION: Qili Qiangxin capsules in addition to comprehensive symptomatic treatment can significantly reduce NT-proBNP level and improve cardiac function in silicosis patients, and thereby improve patients' quality of life.

Functional and morphologic changes in the lungs after a single intratracheal instillation of silica.

The functional and morphologic consequences in the lungs of a single intratracheal instillation of silica dust were evaluated over 6 months. Male Fischer-344 rats were subjected to pulmonary function tests that measured lung volumes, forced expiratory flows, and carbon monoxide diffusing capacity (DLCO). Then saline (0.7 ml, n = 10) or saline containing either 10 mg (n = 9) or 40 mg (n = 14) of silica dust was instilled in the trachea, and each animal was tested 3, 12, and 24 wk later. Morphologic studies were performed on 27 rats similarly treated (3/group/time). By 3 wk after instillation, the inspiratory capacity, forced vital capacity, and DLCO diminished significantly (p less than 0.01) in the high-dose group. After 3 wk, the response tended to level off. Forced expiratory flows were not significantly affected. By contrast, biochemical analysis of lung collagen content indicated a linear accumulation throughout the experimental period. Microscopic evaluation revealed intra-alveolar accumulation of lipoproteinaceous material (alveolar proteinosis) by 3 wk in both dose groups, which persisted through the 24-wk experimental period. A few fibrotic nodules were seen as early as 3 wk in the 40-mg silica group, and their numbers increased with time, whereas they were relatively sparse in the 10-mg silica group throughout the experimental period, despite the diminished functional measurements. These data suggest a closer temporal correlation of the functional decrements observed to the evolution of the alveolar changes than they do to the development of fibrosis. We conclude that the development of nodular fibrosis was not the major contributing factor to the observed functional changes.