title: Suppression of thioredoxin system contributes to silica-induced oxidative stress and pulmonary fibrogenesis in rats.
abstract: 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.
authors: School of Public Health, Capital Medical University, Beijing 100069, China.
authors: Zhonghui
authors: Z
authors: Zhu
authors: Gengxia
authors: G
authors: Yang
authors: Yan
authors: Y
authors: Wang
authors: Jing
authors: J
authors: Yang
authors: Ai
authors: A
authors: Gao
authors: Piye
authors: P
authors: Niu
authors: Lin
authors: L
authors: Tian
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006909:Hydroxyproline / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000032:analysis; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000473:pathology / Q000503:physiopathology; D013880:Thioredoxin-Disulfide Reductase / Q000502:physiology; D013879:Thioredoxins / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D013879:Thioredoxins; D012822:Silicon Dioxide; D013880:Thioredoxin-Disulfide Reductase; D006909:Hydroxyproline
keywords: Pulmonary fibrosis; Silica; Thioredoxin; Thioredoxin reductase