N-acetylcysteine amide (AD4) attenuates oxidative stress in beta-thalassemia blood cells

被引：64

作者：

Amer, Johnny ^{[1
]}

Atlas, Daphne ^{[2
]}

Fibach, Eitan ^{[1
]}

机构：

[1] Hadassah Hebrew Univ, Med Ctr, Dept Hematol, Jerusalem, Israel

[2] Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91905 Jerusalem, Israel

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2008年 / 1780卷 / 02期

关键词：

hemoglobinopathies; free radicals; oxidative stress; N-acetylcysteine amide; reduced glutathione; flow cytometry;

D O I：

10.1016/j.bbagen.2007.11.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：249 / 255

页数：7