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Lab Invest ; 96(12): 1279-1300, 2016 12.
Article in English | MEDLINE | ID: mdl-27775689

ABSTRACT

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.


Subject(s)
Antioxidants/therapeutic use , Disease Models, Animal , Lung/drug effects , Materia Medica/therapeutic use , Oligochaeta/chemistry , Pulmonary Fibrosis/prevention & control , Silicosis/drug therapy , Tissue Extracts/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/administration & dosage , Antioxidants/pharmacology , Apoptosis/drug effects , Cell Line , Cells, Cultured , Epithelial-Mesenchymal Transition/drug effects , Injections, Intraperitoneal , Lung/metabolism , Lung/pathology , Lung/physiopathology , Male , Materia Medica/administration & dosage , Materia Medica/pharmacology , Mice, Inbred C57BL , NF-E2-Related Factor 2/agonists , NF-E2-Related Factor 2/antagonists & inhibitors , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/immunology , RNA Interference , Random Allocation , Respiratory Mucosa/cytology , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Silicosis/metabolism , Silicosis/pathology , Silicosis/physiopathology , Specific Pathogen-Free Organisms , Tissue Extracts/administration & dosage , Tissue Extracts/pharmacology
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