Suppression of thioredoxin system contributes to silica-induced oxidative stress and pulmonary fibrogenesis in rats

• Consecutive study of the process of pulmonary fibrosis induced by silica in vivo.
• Nrf2/Trx axis may be involved in maintaining the redox balance.
• Partly inhibition of Trx activity may result in early oxidative stress.
• Thioredoxin reductase protein was decreased induce by silica in the early days.
• Recovery of redox equilibrium may contribute to alleviation of lung fibrosis

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 (50 mg in 1 ml 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.

The imbalance of redox played an important role in silicosis. At the early period of exposure to silica, the antioxidative regulator, Nrf2 was up-regulated and induced the expression of Trx protein to against ROS. With poor Trx activity (actually with the antioxidant capacity) and down-expression of TrxR in rat lung after silica exposure, oxidative stress could be aggravated, by which promoted the development of silicosis.Figure optionsDownload as PowerPoint slide