Journal
JOURNAL OF PINEAL RESEARCH
Volume 48, Issue 3, Pages 282-289Publisher
WILEY
DOI: 10.1111/j.1600-079X.2010.00752.x
Keywords
antioxidant; cytokines; inflammation; melatonin therapy; muscular dystrophy; oxidative stress; pediatric patients
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Funding
- Instituto de Salud Carlos III [RD06/0013/0008, PI08-1644]
- Servicio Andaluz de Salud [422/2006]
- Consejeria de Innovacion, Ciencia y Empresa, Junta de Andalucia, Spain [P07-CTS-03135, CTS-190, CTS-101]
- Instituto de Salud Carlos III (Spain)
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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)-1 beta, 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, 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.
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