N-acetylcysteine amide (AD4) attenuates oxidative stress in beta-thalassemia blood cells.
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.
Amer
Johnny
J
Department of Hematology, Hadassah - Hebrew University Medical Center, Jerusalem.
Atlas
Daphne
D
Fibach
Eitan
E
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001773:Blood Cells / Q000737:chemistry / Q000187:drug effects*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D017086:beta-Thalassemia / Q000378:metabolism*
D016166:Free Radical Scavengers; C487056:N-Acetylcysteinamide; D005978:Glutathione; D000111:Acetylcysteine