Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy
Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy
复制标题
DOI：
10.1111/j.1600-079x.2010.00752.x
复制
发表时间：
2010-04-01
影响因子：
10.3
通讯作者：
Acuna-Castroviejo, Dario
中科院分区：
文献类型：
--
作者：
Chahbouni, Mariam;Escames, Germaine;Acuna-Castroviejo, Dario
杜氏肌营养不良症（DMD），一种以肌营养不良蛋白缺失为特征的致死性疾病，病程伴慢性炎症、肌上皮损伤和骨骼肌变性。在DMD的多种致病机制中，氧化应激和炎症直接参与了营养不良过程。不幸的是，目前还没有针对DMD的治疗方法，炎症过程是治疗的一个重要目标。基于褪黑素的抗氧化和抗炎特性，我们研究了褪黑素治疗是否可以减少营养不良过程。10例年龄12.8 +/- 0.98岁的DMD患者接受褪黑激素治疗（21:00时60 mg + 09:00时10 mg），并在治疗3、6和9个月时测定血浆脂质过氧化（LPO）、亚硝酸盐（NOx）、白细胞介素(IL)-1 β、IL-2、IL-6、肿瘤坏死因子α、干扰素γ和肌肉损伤血浆标志物的水平。年龄和性别匹配的健康受试者作为对照。结果显示，与对照组相比，DMD患者血浆中LPO、NOx和细胞因子水平显著升高。褪黑素治疗3个月后将这些值降低到控制水平，9个月后进一步降低。与此同时，褪黑素还能降低血浆中肌酸激酶（CK; 50%）、乳酸脱氢酶（28%）、天冬氨酸转氨酶（28%）、丙氨酸转氨酶（20%）和肌红蛋白（13%）的水平。这些发现有力地支持了褪黑素治疗显著减少DMD患者的高氧化和炎症过程，减少肌肉退行性过程的结论。
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.