Effect of N-acetylcysteine plus deferoxamine on oxidative stress and inflammation in dystrophic muscle cells

Author(s)

Rapucci Moraes, Luis Henrique ^[1] ; Bollineli, Roberta Constancio ^[1] ; Mizobuti, Daniela Sayuri ^[1] ; Silveira, Leonardo dos Reis ^{[2, 3]} ; Marques, Maria Julia ^[1] ; Minatel, Elaine ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Biol Estrutural Func, BR-13083970 Campinas, SP - Brazil

^[2] Univ Sao Paulo, FMRP, Dept Bioquim Imunol, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Escola Educ Fis & Esporte Ribeirao Preto, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Redox Report; v. 20, n. 3, p. 109-115, MAY 2015.
• Web of Science Citations: 6

Abstract

Objectives: 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-alpha), and nuclear factor kappa-B (NF-kappa B) 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-alpha (32, 29, and 31%, respectively), and NF-kappa B (34, 38, and 52%, respectively) on dystrophic muscle cells. Discussion: 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-kappa B levels by dystrophic fibers. (AU)

• FAPESP's process: 11/02474-4 - Treatment in vivo and in vitro with calcium blocker and antioxidant in mdx mice
• Grantee: Elaine Minatel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/01087-4 - In vivo and in vitro treatment, with N-acetylcistein and Deferoxamin in dystrophic mouse
• Grantee: Luis Henrique Rapucci Moraes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/07775-0 - Muscle cells of mdx and C57BL/10 mice treated with antioxidants and iron chelating
• Grantee: Roberta Constancio Bollineli
• Support Opportunities: Scholarships in Brazil - Scientific Initiation