title: N-acetylcysteine attenuates subcutaneous administration of bleomycin-induced skin fibrosis and oxidative stress in a mouse model of scleroderma.
abstract: BACKGROUND
  Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of scleroderma, and thus antioxidant therapy may be useful for patients with an impaired oxidative defence mechanism.
  
  
  OBJECTIVE
  To examine the effect of N-acetylcysteine (NAC) on skin fibrosis and oxidative stress in a bleomycin (BLM)-induced mouse model of scleroderma.
  
  
  METHODS
  We used this mouse model to evaluate the effect of NAC on skin fibrosis and oxidative stress. Skin fibrosis was evaluated by histopathological examination and hydroxyproline content. To measure lipid peroxidation, we used a thiobarbituric acid-reactive species, malondialdehyde (MDA). Oxidative protein damage (carbonyl content) and the activities of catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress in the skin tissue.
  
  
  RESULTS
  Treatment with NAC attenuated the skin fibrosis induced by BLM, significantly reducing the MDA and protein carbonyl content in these mice. SOD activity in BLM-only mice and BLM plus NAC-treated mice was increased compared with control mice. However, there was no significant difference in skin SOD activity of mice treated with both BLM and NAC compared with those treated with BLM only. In addition, CAT activity was not altered in the BLM plus NAC mice.
  
  
  CONCLUSIONS
  NAC treatment attenuates skin fibrosis in a BLM-induced mouse model of scleroderma, and this is associated with diminished oxidative stress. The results suggest that NAC may be a potential therapeutic agent for patients with scleroderma.
authors.affiliation: Institute of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
authors.forename: C-F
authors.initials: CF
authors.lastname: Zhou
authors.forename: J-F
authors.initials: JF
authors.lastname: Yu
authors.forename: J-X
authors.initials: JX
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Jiang
authors.forename: S-H
authors.initials: SH
authors.lastname: Xu
authors.forename: Q-Y
authors.initials: QY
authors.lastname: Yu
authors.forename: Q-X
authors.initials: QX
authors.lastname: Zhu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012594:Scleroderma, Localized / Q000188:drug therapy* / Q000378:metabolism; D012867:Skin / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013858:Thiobarbiturates / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D013858:Thiobarbiturates; D001761:Bleomycin; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; C029684:thiobarbituric acid; D000111:Acetylcysteine