TY - JOUR
T1 - N-acetylcysteine amide (AD4) attenuates oxidative stress in beta-thalassemia blood cells
AU - Amer, Johnny
AU - Atlas, Daphne
AU - Fibach, Eitan
PY - 2008/2
Y1 - 2008/2
N2 - Many aspects of the pathology in β-hemoglobinopathies (β-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 β-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 β-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.
AB - Many aspects of the pathology in β-hemoglobinopathies (β-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 β-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 β-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.
KW - Flow cytometry
KW - Free radicals
KW - Hemoglobinopathies
KW - N-acetylcysteine amide
KW - Oxidative stress
KW - Reduced glutathione
UR - http://www.scopus.com/inward/record.url?scp=38549144785&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2007.11.009
DO - 10.1016/j.bbagen.2007.11.009
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C2 - 18082636
AN - SCOPUS:38549144785
SN - 0304-4165
VL - 1780
SP - 249
EP - 255
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 2
ER -