Reduction of Oxidative Damage and Inflammatory Response in the Diaphragm Muscle of mdx Mice Using Iron Chelator Deferoxamine

Author(s)

Rapucci Moraes, Luis Henrique ^[1] ; de Burgos, Rafael Ramos ^[1] ; Macedo, Aline Barbosa ^[1] ; Hermes, Tulio de Almeida ^[1] ; de Faria, Felipe Meira ^[2] ; Minatel, Elaine ^[1]

Affiliation

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

^[2] Univ Estadual Campinas, Inst Biol, Dept Biol Vegetal, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: BIOLOGICAL TRACE ELEMENT RESEARCH; v. 167, n. 1, p. 115-120, SEP 2015.
• Web of Science Citations: 10

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-kappa B 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. (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