title: Earthworm extract attenuates silica-induced pulmonary fibrosis through Nrf2-dependent mechanisms.
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.
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Jingjin
authors: J
authors: Yang
authors: Department of Pathology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors: Ting
authors: T
authors: Wang
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Yan
authors: Y
authors: Li
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Wenxi
authors: W
authors: Yao
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Xiaoming
authors: X
authors: Ji
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Qiuyun
authors: Q
authors: Wu
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Lei
authors: L
authors: Han
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Ruhui
authors: R
authors: Han
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Weiwen
authors: W
authors: Yan
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Jiali
authors: J
authors: Yuan
authors: Department of Occupational Medicine and Environmental Health and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Chunhui
authors: C
authors: Ni
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008419:Materia Medica / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009835:Oligochaeta / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D034622:RNA Interference; D011897:Random Allocation; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012829:Silicosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013047:Specific Pathogen-Free Organisms; D014020:Tissue Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D008419:Materia Medica; D051267:NF-E2-Related Factor 2; D014020:Tissue Extracts