Protandim does not influence alveolar epithelial permeability or intrapulmonary oxidative stress in human subjects with alcohol use disorders
Protandim does not influence alveolar epithelial permeability or intrapulmonary oxidative stress in human subjects with alcohol use disorders
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DOI：
10.1152/ajplung.00171.2011
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发表时间：
2012-04-01
影响因子：
4.9
通讯作者：
Gaydos, Jeanette
中科院分区：
文献类型：
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作者：
Burnham, Ellen L.;McCord, Joe M.;Gaydos, Jeanette
Burnham EL、McCord JM、Bose S、Brown LA、House R、Moss M、Gaydos J。Protandim 不会影响患有酒精使用障碍的人类受试者的肺泡上皮通透性或肺内氧化应激。 Am J Physiol Lung Cell Mol Physiol 302：L688-L699，2012。首次发表于 2012 年 1 月 20 日； doi: 10.1152/ajplung.00171.2011.-酒精使用障碍 (AUD)，包括酒精滥用和酒精依赖，与急性肺损伤 (ALI) 的发生有关。先前的临床研究表明，AUD 与肺氧化应激介导的异常肺泡上皮通透性之间存在关联，这可能部分解释了这种关系。我们试图在 Protandim 的双盲、随机、安慰剂对照试验中确定在 AUD 背景下纠正肺氧化应激是否会使肺泡上皮通透性正常化，Protandim 是一种据报道可以增强抗氧化活性的营养保健品。我们将 30 名健康的 AUD 受试者随机分组，接受直接观察的住院患者口服 Protandim（1,350 毫克/天）或安慰剂治疗。受试者在研究药物给药前和治疗 7 天后接受支气管肺泡灌洗 (BAL) 和血液采样；所有 AUD 受试者均完成了研究方案，且未出现不良事件。在每个时间点测量 BAL 总蛋白作为肺泡上皮通透性的指标。在患有 AUD 的受试者中，在开始研究药物之前，BAL 总蛋白值并未显着高于 11 名同时入组的对照者 (P = 0.07)。在 7 天的研究期间，AUD 受试者的 BAL 总蛋白没有表现出显着变化，无论他们随机分配到 Protandim {n = 14, -2% [四分位范围 (IQR), -56-146%]} 或安慰剂 [n = 16, 77% (IQR -20-290%)； P = 0.19]。此外，在患有 AUD 的患者中，无论接受何种药物类型，BAL 氧化应激指数、上皮生长因子、成纤维细胞生长因子、白细胞介素 1 β 或白细胞介素 10 均未观察到显着变化。在随机接受安慰剂的 AUD 受试者中，血浆硫代巴比妥酸反应物质（脂质过氧化的标志物）随着时间的推移显着下降（P < 0.01）。这些结果表明，新近戒除 AUD 的个体服用 Protandim 7 天不会改变肺泡上皮通透性。然而，我们的工作证明了安全进行临床试验的可行性，其中包括对有急性肺损伤风险的弱势群体进行系列支气管镜检查。
Burnham EL, McCord JM, Bose S, Brown LA, House R, Moss M, Gaydos J. Protandim does not influence alveolar epithelial permeability or intrapulmonary oxidative stress in human subjects with alcohol use disorders. Am J Physiol Lung Cell Mol Physiol 302: L688-L699, 2012. First published January 20, 2012; doi: 10.1152/ajplung.00171.2011.-Alcohol use disorders (AUDs), including alcohol abuse and dependence, have been linked to the development of acute lung injury (ALI). Prior clinical investigations suggested an association between AUDs and abnormal alveolar epithelial permeability mediated through pulmonary oxidative stress that may partially explain this relationship. We sought to determine if correcting pulmonary oxidative stress in the setting of AUDs would normalize alveolar epithelial permeability in a double-blinded, randomized, placebo-controlled trial of Protandim, a nutraceutical reported to enhance antioxidant activity. We randomized 30 otherwise healthy AUD subjects to receive directly observed inpatient oral therapy with either Protandim (1,350 mg/day) or placebo. Subjects underwent bronchoalveolar lavage (BAL) and blood sampling before study drug administration and after 7 days of therapy; all AUD subjects completed the study protocol without adverse events. BAL total protein was measured at each timepoint as an indicator of alveolar epithelial permeability. In subjects with AUDs, before study drug initiation, BAL total protein values were not significantly higher than in 11 concurrently enrolled controls (P = 0.07). Over the 7-day study period, AUD subjects did not exhibit a significant change in BAL total protein, regardless of their randomization to Protandim {n = 14, -2% [intraquartile range (IQR), -56-146%]} or to placebo [n = 16, 77% (IQR -20-290%); P = 0.19]. Additionally, among those with AUDs, no significant changes in BAL oxidative stress indexes, epithelial growth factor, fibroblast growth factor, interleukin-1 beta, or interleukin-10 were observed regardless of drug type received. Plasma thiobarbituric acid reactive substances, a marker of lipid peroxidation, decreased significantly over time among AUD subjects randomized to placebo (P < 0.01). These results suggest that Protandim for 7 days in individuals with AUDs who are newly abstinent does not alter alveolar epithelial permeability. However, our work demonstrates the feasibility of safely conducting clinical trials that include serial bronchoscopies in a vulnerable population at risk for acute lung injury.