The Dietary Supplement Protandim Decreases Plasma Osteopontin and Improves Markers of Oxidative Stress in Muscular Dystrophy Mdx Mice.
The Dietary Supplement Protandim Decreases Plasma Osteopontin and Improves Markers of Oxidative Stress in Muscular Dystrophy Mdx Mice.
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DOI：
10.3109/19390211.2010.482041
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发表时间：
2010-06-01
影响因子：
2.5
通讯作者：
Tseng BS
中科院分区：
文献类型：
--
作者：
Qureshi MM;McClure WC;Arevalo NL;Rabon RE;Mohr B;Bose SK;McCord JM;Tseng BS
杜氏肌营养不良症（DMD）是儿童中最常见和最致命的神经肌肉疾病，其治疗方案仍然难以捉摸。氧化损伤是其发病机制中的相关因素。Protandim®是一种非处方补充剂，具有诱导抗氧化酶的能力。在这项研究中，我们研究了Protandim®是否在DMD的肌营养不良蛋白缺陷（mdx）小鼠模型中使用替代标志物和功能测量提供益处。将雄性3周龄mdx小鼠随机分为两个治疗组：对照组（接受标准啮齿动物食物）和补充Protandim®的标准啮齿动物食物。饮食持续6周和6个月的研究。终点包括氧化应激标志物硫代巴比妥酸反应物质（TBARS）、血浆骨桥蛋白（OPN）、血浆对氧磷酶（PON 1）活性、H&E组织学、腿部肌肉的钆增强磁共振成像（MRI）和运动功能测量。在mdx小鼠中持续6个月的Protandim®食物饮食是安全的并且耐受良好。在Protandim® 6个月后，观察到血浆TBARS平均降低48%;对照组为0.92 nmol/mg蛋白质，而Protandim®组为0.48 nmol/mg蛋白质（p = .006）。在6个月时，Protandim®治疗的小鼠中血浆OPN降低了57%（p = .001）。Protandim®使血浆抗氧化酶PON 1活性增加35%（p = .018）。6个月后，具有Protandim®的mdx小鼠显示出比对照饮食的小鼠少38%的MRI信号异常（p = 0.07）。在这项为期6个月的mdx小鼠研究中，Protandim®未显著改变运动功能或组织学标准。
Therapeutic options for Duchenne muscular dystrophy (DMD), the most common and lethal neuromuscular disorder in children, remain elusive. Oxidative damage is implicated as a pertinent factor involved in its pathogenesis. Protandim® is an over-the-counter supplement with the ability to induce antioxidant enzymes. In this study we investigated whether Protandim® provided benefit using surrogate markers and functional measures in the dystrophin-deficient (mdx)mouse model of DMD. Male 3-week-old mdx mice were randomized into two treatment groups: control (receiving standard rodent chow) and Protandim®-supplemented standard rodent chow. The diets were continued for 6-week and 6-month studies. The endpoints included the oxidative stress marker thiobarbituric acid-reactive substances (TBARS), plasma osteopontin (OPN), plasma paraoxonase (PON1) activity, H&E histology, gadolinium-enhanced magnetic resonance imaging (MRI) of leg muscle and motor functional measurements. The Protandim® chow diet in mdx mice for 6 months was safe and well tolerated. After 6 months of Protandim®, a 48% average decrease in plasma TBARS was seen; 0.92 nmol/mg protein in controls versus 0.48 nmol/mg protein in the Protandim® group (p = .006). At 6 months, plasma OPN was decreased by 57% (p = .001) in the Protandim®-treated mice. Protandim® increased the plasma antioxidant enzyme PON1 activity by 35% (p = .018). After 6 months, the mdx mice with Protandim® showed 38% less MRI signal abnormality (p = .07) than mice on control diet. In this 6-month mdx mouse study, Protandim® did not significantly alter motor function nor histological criteria.