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

Biochim Biophys Acta. 2008 Feb;1780(2):249-55. doi: 10.1016/j.bbagen.2007.11.009. Epub 2007 Nov 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / pharmacology
  • Animals
  • Blood Cells / chemistry
  • Blood Cells / drug effects*
  • Female
  • Free Radical Scavengers / pharmacology*
  • Glutathione / analysis
  • Hemolysis / drug effects
  • Humans
  • Male
  • Mice
  • Oxidative Stress / drug effects*
  • Phagocytosis / drug effects
  • beta-Thalassemia / metabolism*


  • Free Radical Scavengers
  • N-Acetylcysteinamide
  • Glutathione
  • Acetylcysteine