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

Abstract

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.

• Authors: Johnny Amer, Daphne Atlas, Eitan Fibach
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1780 Issue 2 Pg. 249-55 (Feb 2008) ISSN: 0006-3002 [Print] Netherlands
• PMID: 18082636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Acetylcysteine (analogs & derivatives, pharmacology)
• Animals
• Blood Cells (chemistry, 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)