N-acetylcysteine tiherapeutically protects against pulmonary fibrosis in a mouse model of silicosis.

Huaping Huang,Xi Li,Meihua Liu,Jie Wang,Mingjing Chen,Feng Liu,Jialiang Chen,Haifeng Wu

doi:10.1042/bsr20190681

Abstract

Silicosis is a lethal pneumoconiosis disease characterized by chronic lung inflammation and fibrosis. The present study was to explore the effect of against crystalline silica (CS)-induced pulmonary fibrosis. A total of 138 wild-type C57BL/6J mice were divided into control and experimental groups, and killed on month 0, 1, 2, 3, 4, and 5. Different doses of N-acetylcysteine (NAC) were gavaged to the mice after CS instillation to observe the effect of NAC on CS induced pulmonary fibrosis and inflammation. The pulmonary injury was evaluated with Hematoxylin and eosin/Masson staining. Reactive oxygen species level was analyzed by DCFH-DA labeling. Commercial ELISA kits were used to determine antioxidant activity (T-AOC, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) and cytokines (TNF-α, IL-1β, IL-4, and IL-6). The expression of oxidising enzymes (NOX2, iNOS, SOD2, and XO) were detected by real time PCR. Immunohistochemistry (IHC) staining was performed to examine epithelial-mesenchymal transition-related markers. The mice treated with NAC presented markedly reduced CS-induced pulmonary injury and ameliorated CS-induced pulmonary fibrosis and inflammation. The level of malondialdehyde was reduced, while the activities of GSH-PX, SOD, and T-AOC were markedly enhanced by NAC. We also found the down-regulation of oxidising enzymes (NOX2, iNOS, SOD2, and XO) after NAC treatment. Moreover, E-cadherin expression was increased while vimentin and Cytochrome C expressions were decreased by NAC. These encouraging findings suggest that NAC exerts pulmonary protective effects in CS-induced pulmonary fibrosis and might be considered as a promising agent for the treatment of silicosis.

Highlights

Silicosis is considered as one of the serious types of pneumoconiosis and a potentially fatal occupational fibrotic lung disease [1], which is highly prevalent in developing countries, especially in China, South Africa, and Brazil [2]
As a type of chronic pulmonary diseases, is a progressive occupational lung disease caused by the long-term inhalation, deposition, and retention of crystalline silica (CS) particles [28]
We established a mouse silicosis model by chronic exposure to CS in order to investigate the possible effects of NAC on the CS-induced chronic pulmonary disease

Summary

Introduction

Silicosis is considered as one of the serious types of pneumoconiosis and a potentially fatal occupational fibrotic lung disease [1], which is highly prevalent in developing countries, especially in China, South Africa, and Brazil [2]. The increasing mortality of silicosis has made silica exposure a high-priority public health concern in countries worldwide [5]. When respirable CS particles are inhaled, their entry into alveoli induces oxidative stress through the formation of reactive oxygen (ROS) and nitrogen species due to the generation of siloxil radicals after crystalline-silica fracturing [8]. It leads to extensive fibroblast proliferation and deposition of extracellular matrix (ECM) with the lungs and further triggers cytotoxicity, oxidative stress, pulmonary inflammation, and eventually silicosis [9]. The progression of lung fibrosis is accompanied with infiltration of inflammatory cells including eosinophils, License 4.0 (CC BY)

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