title: Reduction of Oxidative Damage and Inflammatory Response in the Diaphragm Muscle of mdx Mice Using Iron Chelator Deferoxamine.
abstract: Oxidative stress and inflammatory processes strongly contribute to pathogenesis in Duchenne muscular dystrophy (DMD). Based on evidence that excess iron may increase oxidative stress and contribute to the inflammatory response, we investigated whether deferoxamine (DFX), a potent iron chelating agent, reduces oxidative stress and inflammation in the diaphragm (DIA) muscle of mdx mice (an experimental model of DMD). Fourteen-day-old mdx mice received daily intraperitoneal injections of DFX at a dose of 150 mg/kg body weight, diluted in saline, for 14 days. C57BL/10 and control mdx mice received daily intraperitoneal injections of saline only, for 14 days. Grip strength was evaluated as a functional measure, and blood samples were collected for biochemical assessment of muscle fiber degeneration. In addition, the DIA muscle was removed and processed for histopathology and Western blotting analysis. In mdx mice, DFX reduced muscle damage and loss of muscle strength. DFX treatment also resulted in a significant reduction of dystrophic inflammatory processes, as indicated by decreases in the inflammatory area and in NF-κB levels. DFX significantly decreased oxidative damage, as shown by lower levels of 4-hydroxynonenal and a reduction in dihydroethidium staining in the DIA muscle of mdx mice. The results of the present study suggest that DFX may be useful in therapeutic strategies to ameliorate dystrophic muscle pathology, possibly via mechanisms involving oxidative and inflammatory pathways.
authors.affiliation: Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil.
authors.forename: Luis Henrique Rapucci
authors.initials: LH
authors.lastname: Moraes
authors.forename: Rafael Ramos
authors.initials: RR
authors.lastname: de Burgos
authors.forename: Aline Barbosa
authors.initials: AB
authors.lastname: Macedo
authors.forename: Tulio
authors.initials: T
authors.lastname: de Almeida Hermes
authors.forename: Felipe Meira
authors.initials: FM
authors.lastname: de Faria
authors.forename: Elaine
authors.initials: E
authors.lastname: Minatel
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000517:prevention & control; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000517:prevention & control*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D007502:Iron Chelating Agents; D016328:NF-kappa B; D003676:Deferoxamine