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阿朴啡因可降低健康受试者呼气中过氧化氢和硝酸盐的浓度。

Apocynin decreases hydrogen peroxide and nitrate concentrations in exhaled breath in healthy subjects.

机构信息

Department of Immunopathology, Medical University of Lodz, 251 Pomorska Street, Building C5, 92 213 Lodz, Poland.

出版信息

Pulm Pharmacol Ther. 2010 Feb;23(1):48-54. doi: 10.1016/j.pupt.2009.09.003. Epub 2009 Sep 25.

Abstract

The imbalance between reactive oxygen species (ROS) synthesis and antioxidants might be involved in the pathogenesis of many inflammatory diseases. NADPH oxidase, an enzyme responsible for ROS production, may represent an attractive therapeutic target to inhibit, for the treatment of these diseases. Apocynin is an inhibitor of activation of NADPH oxidase complex present in the inflammatory cells. In double blind, placebo-controlled, cross-over study, we investigated the effect of nebulized apocynin on ROS synthesis in 10 nonsmoking healthy volunteers. Apocynin (6ml of 0.5mg/ml) was administered by nebulization and its effects on H(2)O(2), NO(2)(-) and NO(3)(-) generation were assessed after 30, 60 and 120min by collecting exhaled breath condensate (EBC) samples using an EcoScreen analyzer. Additionally, respiratory parameters have been evaluated, utilizing spirometry and DLCO. We also analyzed peripheral blood differential counts and NO(2)(-) serum level, cough scale control and blood pressure as safety parameters. Apocynin caused reduction of H(2)O(2) concentration in EBC as compared to placebo, after 60min. of inhalation (0.18microM vs. 0.31microM, p<0.05) as well as after 120min. (0.2microM vs. 0.31microM, p<0.05). Similarly, apocynin significantly decreased concentration of NO(3)(-) as compared to placebo, after 60 and 120min. (6.8microM vs. 14.4microM and 6.5microM vs. 14.9microM respectively, p<0.05). Apocynin was well tolerated and no adverse events have been observed throughout the study. Thus, as apocynin significantly influence ROS concentration, it might have also antiinflammatory properties. As it is safe, it may have a potential to become a drug in airway inflammatory diseases treatment.

摘要

活性氧(ROS)的合成和抗氧化剂之间的失衡可能与许多炎症性疾病的发病机制有关。NADPH 氧化酶是一种负责 ROS 产生的酶,可能代表一种有吸引力的治疗靶点,以抑制这些疾病。阿朴肉桂酸是一种存在于炎症细胞中的 NADPH 氧化酶复合物的激活抑制剂。在一项双盲、安慰剂对照、交叉研究中,我们调查了雾化阿朴肉桂酸对 10 名不吸烟健康志愿者 ROS 合成的影响。阿朴肉桂酸(6ml 浓度为 0.5mg/ml)通过雾化给药,在 30、60 和 120 分钟后通过使用 EcoScreen 分析仪收集呼气冷凝物(EBC)样本来评估其对 H2O2、NO2-和 NO3-生成的影响。此外,利用肺活量计和 DLCO 评估呼吸参数。我们还分析了外周血差异计数和血清 NO2-水平、咳嗽量表控制和血压作为安全参数。与安慰剂相比,阿朴肉桂酸在吸入 60 分钟后使 EBC 中的 H2O2 浓度降低(0.18μM 对 0.31μM,p<0.05),120 分钟后也降低(0.2μM 对 0.31μM,p<0.05)。同样,与安慰剂相比,阿朴肉桂酸在 60 和 120 分钟后也显著降低了 NO3-的浓度(分别为 6.8μM 对 14.4μM 和 6.5μM 对 14.9μM,p<0.05)。阿朴肉桂酸耐受性良好,整个研究过程中未观察到不良反应。因此,由于阿朴肉桂酸显著影响 ROS 浓度,它可能也具有抗炎特性。由于它是安全的,它可能有潜力成为治疗气道炎症性疾病的药物。

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