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

Biosci Rep. 2019 Jul 18;39(7):BSR20190681. doi: 10.1042/BSR20190681. Print 2019 Jul 31.

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.

Keywords: N-acetylcysteine; Silicosis; anti-inflammation; antioxidation; pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Administration, Oral
  • Animals
  • Antioxidants / pharmacology*
  • Crystallization
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation / drug effects
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • NADPH Oxidase 2 / genetics
  • NADPH Oxidase 2 / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / drug effects
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control*
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Silicon Dioxide / administration & dosage
  • Silicosis / etiology
  • Silicosis / genetics
  • Silicosis / pathology
  • Silicosis / prevention & control*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Xanthine Oxidase / genetics
  • Xanthine Oxidase / metabolism

Substances

  • Antioxidants
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Interleukin-4
  • Silicon Dioxide
  • Glutathione Peroxidase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Xanthine Oxidase
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • Acetylcysteine