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

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 (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.

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…Melatonin (300 mg/day for up to 3 years) decreased oxidative stress in patients with amyotrophic lateral sclerosis [211] with very few undesirable side effects. In children with muscular dystrophy, 70 mg/day of melatonin reduced cytokines and lipid peroxidation [212]. Doses of 80 mg melatonin hourly for 4 h were given to healthy men with no undesirable effects other than drowsiness [213].…”

Melatonin inhibits IL1β-induced MMP9 expression and activity in human umbilical vein endothelial cells by suppressing NF-κB activation

“…Melatonin has pleiotropic bioactivities including as a highly effective antioxidant and free radical scavenger (Beyer et al 1998, Gitto et al 2009, Chahbouni et al 2010, Paradies et al 2010. Melatonin has protective effect against heart and brain ischemia/reperfusion injuries depending on its antioxidant and free radical scavenging properties (Paradies et al 2010).…”

Melatonin Reduces Hypoglycemia-Induced Neuronal Death in Rats

“…Melatonin has a strong ability to suppress inflammation and modulate immune responses [14,38]. Melatonin has been shown to attenuate microglial activation after ischemia [39].…”

“…Several studies have shown that melatonin has free radical scavenging and antioxidant functions [13]. It has the capability of scavenging free radicals and blocking transcription factors that induce proinflammatory cytokines [14]. These functions contribute to melatonin's antioxidant and anti-inflammatory properties in the diabetic setting [15].…”