Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy

Authors

  • Mariam Chahbouni,

    1. Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain
    2. Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
    Search for more papers by this author
  • Germaine Escames,

    1. Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain
    2. Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
    Search for more papers by this author
  • Carmen Venegas,

    1. Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain
    2. Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
    Search for more papers by this author
  • Belén Sevilla,

    1. Unidad de Gestión Clínica de Pediatría, Hospital Universitario San Cecilio, Granada, Spain
    Search for more papers by this author
  • José Antonio García,

    1. Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain
    2. Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
    Search for more papers by this author
  • Luis C. López,

    1. Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain
    2. Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
    Search for more papers by this author
  • Antonio Muñoz-Hoyos,

    1. Unidad de Gestión Clínica de Pediatría, Hospital Universitario San Cecilio, Granada, Spain
    Search for more papers by this author
  • Antonio Molina-Carballo,

    1. Unidad de Gestión Clínica de Pediatría, Hospital Universitario San Cecilio, Granada, Spain
    Search for more papers by this author
  • Darío Acuña-Castroviejo

    1. Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain
    2. Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
    3. Servicio de Análisis Clínicos, Hospital Universitario San Cecilio, Granada, Spain
    Search for more papers by this author

Address reprint requests to Dario Acuña-Castroviejo, Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain.
E-mail: dacuna@ugr.es; or Antonio Molina-Carballo, Servicio de Pediatría, Hospital Universitario San Cecilio, Avenida Dr. Olóriz 12, 18012 Granada, Spain.
E-mail: amolinac@ugr.es

Abstract

Abstract:  Duchenne muscular dystrophy (DMD), a lethal disorder characterized by dystrophin absence, courses with chronic inflammation, sarcolemmal damage, and skeletal muscle degeneration. Among the multiple pathogenic mechanisms proposed for DMD, oxidative stress and inflammation are directly involved in the dystrophic process. Unfortunately, there is no current treatment for DMD, and the inflammatory process is an important target for therapies. Based on the antioxidant and anti-inflammatory properties of melatonin, we investigated whether melatonin treatment may reduce the dystrophic process. Ten DMD patients aged 12.8 ± 0.98 yr, were treated with melatonin (60 mg at 21:00 hr plus 10 mg at 09:00 hr), and plasma levels of lipid peroxidation (LPO), nitrites (NOx), interleukin (IL)-1β, IL-2, IL-6, tumor necrosis factor-α, interferon-γ, and plasma markers of muscle injury, were determined at 3, 6 and 9 months of treatment. Healthy age- and sex-matched subjects were used as controls. The results show a significant increase in LPO, NOx, and cytokine levels in plasma of DMD patients compared with controls. Melatonin administration reduced these values to control levels at 3 months of treatment, decreasing further 9 months later. In parallel, melatonin also reduced plasma levels of creatine kinase (CK; 50%), lactate dehydrogenase (28%), aspartate aminotransferase (28%), alanine aminotransferase (20%), and myoglobin (13%). These findings strongly support the conclusion that melatonin administration significantly reduced the hyperoxidative and inflammatory process in DMD patients, reducing the muscle degenerative process.

Ancillary