N-acetylcysteine amide (AD4) attenuates oxidative stress in beta-thalassemia blood cells
N-acetylcysteine amide (AD4) attenuates oxidative stress in beta-thalassemia blood cells
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DOI：
10.1016/j.bbagen.2007.11.009
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发表时间：
2008-02-01
影响因子：
3
通讯作者：
Fibach, Eitan
中科院分区：
文献类型：
--
作者：
Amer, Johnny;Atlas, Daphne;Fibach, Eitan
β -血红蛋白病（β -地中海贫血和镰状细胞性贫血）病理的许多方面是由氧化应激介导的。在本研究中，我们测试了一种新的硫醇化合物，n -乙酰半胱氨酸（NAC）的酰胺形式n -乙酰半胱氨酸酰胺（AD4）的抗氧化作用。通过流式细胞术，我们发现体外处理AD4 β -地中海贫血患者的血细胞可提高红细胞（RBC）、血小板和多形核（PMN）白细胞的还原性谷胱甘肽（GSH）含量，并降低其ROS。这些作用导致地中海贫血红细胞对巨噬细胞溶血和吞噬的敏感性显著降低。腹腔注射AD4 （150 mg/kg）可降低β -地中海贫血小鼠的氧化应激参数（p < 0.001）。我们的研究结果表明，与NAC相比，AD4在体外和体内都具有降低地中海贫血细胞氧化应激标志物的优势。(C) 2007 Elsevier B.V.版权所有
Many aspects of the pathology in beta-hemoglobinopathies (beta-thalassemia and sickle cell anemia) are mediated by oxidative stress. In the present study we tested a novel thiol compound, N-acetylcysteine amide (AD4), the amide form of N-acetyl cysteine (NAC) for its antioxidant effects. Using flow-cytometry, we showed that in vitro treatment of blood cells from beta-thalassemic patients with AD4 elevated the reduced glutathione (GSH) content of red blood cells (RBC), platelets and polymorphonuclear (PMN) leukocytes, and reduced their ROS. These effects resulted in a significant reduced sensitivity of thalassemic RBC to hemolysis and phagocytosis by macrophages. Intra-peritoneal injection of AD4 to beta-thalassemic mice (150 mg/kg) reduced the parameters of oxidative stress (p < 0.001). Our results show the superiority of AD4, compared to NAC, in reducing oxidative stress markers in thalassemic cells both in vitro and in vivo. (C) 2007 Elsevier B.V. All rights reserved.