Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy.
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 (NO(x)), interleukin (IL)-1beta, IL-2, IL-6, tumor necrosis factor-alpha, interferon-gamma, 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, NO(x), 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.
Chahbouni
Mariam
M
Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain.|Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
Escames
Germaine
G
Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain.|Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
Venegas
Carmen
C
Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain.|Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
Sevilla
Belén
B
Unidad de Gestión Clínica de Pediatría, Hospital Universitario San Cecilio, Granada, Spain.
García
José Antonio
JA
Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain.|Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
López
Luis C
LC
Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain.|Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
Muñoz-Hoyos
Antonio
A
Unidad de Gestión Clínica de Pediatría, Hospital Universitario San Cecilio, Granada, Spain.
Molina-Carballo
Antonio
A
Unidad de Gestión Clínica de Pediatría, Hospital Universitario San Cecilio, Granada, Spain.
Acuña-Castroviejo
Darío
D
Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Armilla, Granada, Spain.|Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.|Servicio de Análisis Clínicos, Hospital Universitario San Cecilio, Granada, Spain.
D000293:Adolescent; D000704:Analysis of Variance; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008550:Melatonin / Q000097:blood / Q000627:therapeutic use*; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000188:drug therapy*; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*
D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D008550:Melatonin