title: N-Acetyl cysteine (NAC) inhibits proliferation, collagen gene transcription, and redox stress in rat palatal mucosal cells.
abstract: OBJECTIVE
  Control of hyperplastic and invasively growing gingival tissue is crucial for maintaining normal oral function and for successful bone regenerative therapy. We tested the hypothesis that materials containing N-acetyl cysteine (NAC), an antioxidant cysteine derivative, can control proliferation and function of oral mucosal cells.
  
  
  METHODS
  Oral mucosal cells derived from the rat palatal tissue were cultured with or without NAC at different concentrations (2.5-10.0mM). To simulate inflammatory conditions, cultures were treated with hydrogen peroxide. NAC was also applied via collagen materials in membrane and sponge forms to explore the clinical applicability. The redox balance inside the cells was evaluated by measuring the concentration of intracellular glutathione (GSH).
  
  
  RESULTS
  Adding NAC into cultures of oral mucosal cells reduced their proliferation, transcriptional expression, and collagen production in an NAC-concentration-dependent manner without cytotoxic effects. Furthermore, NAC substantially reduced the hydrogen peroxide-induced elevation of cellular proliferation and collagen production. The controlling effects of NAC were also demonstrated in cells cultured on NAC-containing collagen materials and were associated with an increase in intracellular glutathione (GSH) reserves and a decrease in the oxidized form of glutathione (GSSG).
  
  
  CONCLUSIONS
  These results indicate that NAC may abrogate inflammation- or oxidative-stress-induced hyperfunction of oral mucosal cells and that it can be delivered effectively via biodegradable materials. This study provides a basis to explore NAC-containing biomaterials that are functionalized to control oral soft tissue growth and function without cytotoxicity.
authors.affiliation: Laboratory of Bone and Implant Sciences (LBIS), Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Ueno
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Tsukimura
authors.forename: W
authors.initials: W
authors.lastname: Att
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: N
authors.initials: N
authors.lastname: Hori
authors.forename: H
authors.initials: H
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Ogawa
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D024042:Collagen Type I / Q000032:analysis / Q000037:antagonists & inhibitors; D024061:Collagen Type III / Q000032:analysis / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D011393:Procollagen-Proline Dioxygenase / Q000032:analysis / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D024042:Collagen Type I; D024061:Collagen Type III; D004337:Drug Carriers; D016166:Free Radical Scavengers; D016877:Oxidants; D003094:Collagen; D006861:Hydrogen Peroxide; C510863:P4HA1 protein, human; D011393:Procollagen-Proline Dioxygenase; D005978:Glutathione; D000111:Acetylcysteine