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

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.

Astragaloside IV alleviates silica‑induced pulmonary fibrosis via inactivation of the TGF‑β1/Smad2/3 signaling pathway

“…Accumulating evidence has indicated that silica induces inflammatory responses, including the secretion of inflammatory factors (26) and infiltration of inflammatory cells (27). In the present study, it was shown that in the silicosis group, total cell counts, as well as the neutrophil, lymphocyte and macrophage counts were high.…”

“…It reflects the quantities of oxidized free radicals in the body to a certain extent, and indirectly reflects the degree of oxidative stress, which is negatively correlated with lung function (34), and may lead to irreversible lung injury (27). Antioxidants, such as GSH-px and SOD, can not only resist the direct damage caused by oxidants, but also alters the course of inflammatory events associated with chronic lung diseases (27). In the present study, following exposure to silica, there was a significant decrease in GSH-px and SOD levels, as well as a significant increase in the levels of ROS and MDA in silicotic patients.…”

Airway Hygiene in COVID-19 Pneumonia: Treatment Responses of 3 Critically Ill Cruise Ship Employees

“…In a Cochrane review, patients with ARDS who were administered NAC spent less time in the ICU [ 46 ]. In animal models, NAC has been shown to have a protective effect against pulmonary fibrosis [ 47 , 48 ]. Currently, a clinical trial is being conducted on the effectiveness of NAC in critically ill patients with COVID-19 [ 49 ].…”

New Insights into Pathomechanisms and Treatment Possibilities for Lung Silicosis

“…Anakinra, given to the 37-year-old man in a dose of 100 mg/day subcutaneously for 6 months, improved his respiratory functions, oxygen saturation, and inflammatory markers (C-reactive protein, erythrocyte sedimentation rate) [95]. Anti CD-11 antibodies [103] Agents influencing autophagy-lysosomal system Imipramine [104] Dioscin [105] Rapamycin/cAMP [106] Atractylenolide III [107] Trehalose [108] Antioxidants N-acetylcysteine [109][110][111] Corticosteroids Dexamethasone [112][113][114][115] Flunisolide [116] Endogenous glucocorticoids Annexin A1 [117] Agents increasing cAMP Roflumilast [118] Tadalafil [119] Sildenafil [115] Agents influencing TGFβ Emodin [120,121] Ponatinib [122] Table 1. Cont.…”