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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Redox Report; v. 20, n. 3, p. 109-115, MAY 2015.
• Citações Web of Science: 6

Resumo

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)

• Processo FAPESP: 11/51697-6 - Mecanismos de acao do acido eicosapentanoico (epa) na protecao a mionecrose em fibras musculares distroficas
• Beneficiário: Maria Julia Marques
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/02474-4 - Tratamento in vivo e in vitro com bloqueador de cálcio e antioxidante em camundongos mdx
• Beneficiário: Elaine Minatel
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/01087-4 - Tratamento in vivo e in vitro com a associação de N-acetilcisteína e deferoxamina em camundongos distróficos
• Beneficiário: Luis Henrique Rapucci Moraes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/07775-0 - Células musculares de camundongos das linhagens mdx e C57BL/10 tratadas com antioxidantes e quelante de ferro
• Beneficiário: Roberta Constancio Bollineli
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 07/50189-1 - Influencia do acido ascorbico no processo de degeneracao muscular em camundongos distroficos.
• Beneficiário: Elaine Minatel
• Modalidade de apoio: Auxílio à Pesquisa - Regular