title: High-dose N-acetylcysteine decreases silica-induced lung fibrosis in the rat.
abstract: OBJECTIVE
  To study the potential of high-dose N-acetylcysteine (NAC) to attenuate silica-induced pulmonary fibrosis in the rat.
  
  
  METHODS
  Rats exposed to intratracheal instillation of silica particles were treated with 500 mg/kg NAC orally every day for 7 days, before and up to 28 days after silica administration (n = 32), or received no treatment following silica exposure (n = 32); a third group received intratracheal saline (n = 32). Fibrosis score, and hydroxyproline (HYP) and malondialdehyde (MDA) content, were assessed in lung tissue. Bronchoalveolar lavage fluid (BALF) and serum levels of tumour necrosis factor (TNF)-α, interleukin (IL)-8 and high-sensitivity C-reactive protein (hsCRP) were assessed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Histopathology revealed inflammation and fibrosis in lung tissue from rats exposed to silica, but not in saline controls. The fibrosis score was significantly lower in animals treated with NAC compared with silica-exposed untreated rats. HYP and MDA content were significantly lower at all timepoints, following NAC treatment versus no treatment, in silica-exposed rats. NAC attenuated silica-induced increases in TNF-α, IL-8 and hsCRP in BALF and serum.
  
  
  CONCLUSIONS
  Oral treatment with high-dose NAC during early silica exposure can ameliorate the activity of proinflammatory cytokines, thus attenuating subsequent lung fibrosis. These results suggest that NAC has potential as a treatment for silica-induced lung fibrosis.
authors.affiliation: Department of Respiratory Medicine, Qingdao Central Hospital, Qingdao, Shandong, China. ghd1998@126.com
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Yin
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D012822:Silicon Dioxide; D002097:C-Reactive Protein; D006909:Hydroxyproline; D000111:Acetylcysteine
keywords: Lung fibrosis; N-acetylcysteine; rat model; silicosis