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

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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.

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Acknowledgments

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grants 08/50731-3 and 11/02474-4). A.B.M. and T.A.H. are the recipients of a CAPES fellowship, F.M.F was the recipient of a CAPES PNPD fellowship, and L.H.R.M. was the recipient of a FAPESP (grant 10/01087-4) fellowship.

Conflict of Interest

All the authors declare that they do not have any conflict of interest.

Statement of Authorship

LHRM conducted the study. LHRM, RRB, ABM, TAH, and FMF analyzed the data and performed the statistical analysis. EM participated in the design of the study and coordination. EM and LHRM helped draft the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, 13083-970, Brazil

    Luis Henrique Rapucci Moraes, Rafael Ramos de Burgos, Aline Barbosa Macedo, Tulio de Almeida Hermes & Elaine Minatel

  2. Departamento de Biologia Vegetal, Instituto de Biologia, Universidade estadual de Campinas, Campinas, SP, 13083-970, Brazil

    Felipe Meira de Faria

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  1. Luis Henrique Rapucci Moraes
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  2. Rafael Ramos de Burgos
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  3. Aline Barbosa Macedo
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  4. Tulio de Almeida Hermes
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  5. Felipe Meira de Faria
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  6. Elaine Minatel
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Correspondence to Elaine Minatel.

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Moraes, L.H.R., de Burgos, R.R., Macedo, A.B. et al. Reduction of Oxidative Damage and Inflammatory Response in the Diaphragm Muscle of mdx Mice Using Iron Chelator Deferoxamine. Biol Trace Elem Res 167, 115–120 (2015). https://doi.org/10.1007/s12011-015-0290-y

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