title: Effect of N-acetylcysteine plus deferoxamine on oxidative stress and inflammation in dystrophic muscle cells.
abstract: OBJECTIVE
  Oxidative stress and inflammatory process play an important role in the pathogenesis of Duchenne muscular dystrophy (DMD). We investigated whether deferoxamine (DFX) improves the antioxidant effects of N-acetylcysteine (NAC) on primary cultures of dystrophic muscle cells from mdx mice, the experimental model of DMD.
  
  
  METHODS
  Primary cultures of skeletal muscle cells from mdx mice were treated with either NAC (10 mM), DFX (5 mM), or NAC plus DFX for 24 hours. The muscle cells of C57BL/10 mice were used as controls.
  
  
  RESULTS
  Production of hydrogen peroxide (H2O2) and levels of 4-hydroxynonenal (4-HNE), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa-B (NF-κB) were significantly higher in mdx muscle cells than in C57BL/10 muscle cells. Treatment with NAC, DFX, or NAC plus DFX significantly decreased H2O2 production (24, 58, and 72%, respectively), and levels of 4-HNE-protein adducts (62, 33, and 71%, respectively), TNF-α (32, 29, and 31%, respectively), and NF-κB (34, 38, and 52%, respectively) on dystrophic muscle cells.
  
  
  CONCLUSIONS
  This study demonstrates that mdx muscle cells are able to produce key oxidative stress and inflammatory markers, without the interference of inflammatory cells, and shows that NAC plus DFX reduced the inflammatory and oxidative stress indicators, mainly H2O2 production and NF-κB levels by dystrophic fibers.
authors.forename: Luis Henrique Rapucci
authors.initials: LH
authors.lastname: Moraes
authors.forename: Roberta Constâncio
authors.initials: RC
authors.lastname: Bollineli
authors.forename: Daniela Sayuri
authors.initials: DS
authors.lastname: Mizobuti
authors.forename: Leonardo Dos Reis
authors.initials: Ldos R
authors.lastname: Silveira
authors.forename: Maria Julia
authors.initials: MJ
authors.lastname: Marques
authors.forename: Elaine
authors.initials: E
authors.lastname: Minatel
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000447:Aldehydes; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D003676:Deferoxamine; C027576:4-hydroxy-2-nonenal; D000111:Acetylcysteine
keywords: Deferoxamine; Duchenne muscular dystrophy; Dystrophic fibers; Inflammatory markers; N-acetylcysteine; Oxidative stress; mdx Mice