Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Silicosis is one of the most prevalent occupational lung diseases worldwide. This study aimed to investigate the possible mechanism that silica affected thioredoxin (Trx) system during the development of silicosis in vivo. Male Wistar rats were randomly divided into saline group and silica group in which rats were intratracheally instilled with a single dose of silica suspension (50mg in 1ml saline/rat). After 7, 15 or 30 days instillation, rats were sacrificed. Biochemical parameters and histopathology were assessed. Our results demonstrated that silica could significantly cause the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) as well as activate antioxidative protein Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream protein Trx in the early exposure to silica. The inhibition of Trx activity and the down-regulated expression of thioredoxin reductase (TrxR), suggesting that the function of Trx system may be suppressive induced by silica. Content of lung hydroxyproline and histopathological results showed significant fibrosis development with time. In conclusion, our study demonstrated that silica could suppress the Trx system to perturb the redox balance, elicit oxidative stress, and eventually induce pulmonary fibrosis.
...
PMID:Suppression of thioredoxin system contributes to silica-induced oxidative stress and pulmonary fibrogenesis in rats. 2397 37

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.
 ...
PMID:Earthworm extract attenuates silica-induced pulmonary fibrosis through Nrf2-dependent mechanisms. 2777 89

Alveolar macrophages are believed to induce oxidative stress via reactive oxygen species (ROS) when silica particles are inhaled. This process can contribute to the pathogenesis of silicosis, but the mechanism is unclear. A traditional Chinese herbal derivative, sodium tanshinone IIA sulfonate (STS), displays significant antioxidant effects. Here, we determine whether STS can attenuate the oxidative stress induced by silica. Traditionally, studies on the toxic effects of silica have focused on monocultures of macrophages or fibroblasts. A coculture model of macrophages (Raw 264.7) and pulmonary fibroblasts (MRC-5) was used in this study to mimic a more in vivo-like environment. We investigated the protective effects of STS on the abnormal proliferation of MRC-5 fibroblasts in an in vitro model. The results showed that fibroblast viability increased with the accumulation of intracellular ROS induced by cocultured Raw 264.7 cells after silica exposure. Treatment with STS markedly ameliorated the silica-induced cell proliferation and oxidative stress. Western blotting and immunofluorescence analysis of the Nrf2 and thioredoxin (Trx) system were conducted, and the results confirmed that treatment with STS enhanced nuclear Nrf2 accumulation and mediated antioxidant Trx system expression. These findings suggest that silica exposure might induce some level of oxidative stress in fibroblasts and that STS might augment antioxidant activities via up-regulation of the Nrf2 and Trx system pathways in MRC-5 cells in vitro.
 ...
PMID:Sodium tanshinone IIA sulfonate suppresses pulmonary fibroblast proliferation and activation induced by silica: role of the Nrf2/Trx pathway. 3009 Mar 31

Silicosis is characterized by pulmonary fibrosis due to long-term inhalation of silica particles. Although the cause of this serious disease is known, its pathogenesis remains unclear and there are currently no specific treatments. Recent studies have shown that the anti-oxidant transcription factor Nrf2 is expressed at reduced levels in fibrotic foci, which may be related to disease progression. However, the molecular mechanisms by which this might occur have yet to be elucidated. Sodium tanshinone IIA sulfonate (STS), an extract of Salvia miltiorrhiza, is used in traditional Chinese medicine in the treatment of coronary heart disease. STS has been shown to play a strong anti-oxidative role in various organs. Here, we employed a rat model to explore the effects of STS on oxidative stress and the progression of fibrosis in silicosis. STS significantly reduced collagen deposition in the lungs, thereby antagonising silicosis. Immunohistochemical and immunofluorescence staining showed that Nrf2 was differentially expressed in lung cells during silica induced fibrosis, and chromatin immunoprecipitation-sequencing experiments demonstrated that Nrf2 promoted the expression of the antioxidant proteins thioredoxin and thioredoxin reductase. Our results suggest that the anti-fibrotic effects of STS may be related to upregulation of Nrf2 nuclear expression, especially in fibrotic lesions, and the promotion of thioredoxin and thioredoxin reductase expression. Our findings may open up new avenues for the development of STS as a treatment for silicosis.
 ...
PMID:Sodium tanshinone IIA sulfonate attenuates silica-induced pulmonary fibrosis in rats via activation of the Nrf2 and thioredoxin system. 3273 94