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Plasmodium falciparum: Activity of artemisinin against Plasmodium falciparum cultured in sickle trait hemoglobin AS and normal hemoglobin AA red blood cells
Authors:Walcourt A  Kurantsin-Mills J  Adenuga B B  Loyevsky M  Kassim O O  Gordeuk V R
Institution:aDepartment of Physiology & Biophysics, Howard University College of Medicine, 520 W Street, Seely G Mudd Building, NW, Washington, DC 20059, USA;bCenter for Sickle Cell Disease, Howard University College of Medicine, NW, Washington, DC 20059, USA;cDepartment of Microbiology, Howard University College of Medicine, NW, Washington, DC 20059, USA;dDepartment of Medicine, Howard University College of Medicine, NW, Washington, DC 20059, USA
Abstract:The presence of sickle hemoglobin causes accumulation of hemoglobin degradative products that favor oxidative reaction in erythrocytes. Artemisinin derivatives exert antiparasite effects through oxidative reactions within infected erythrocytes. Using 3H]-hypoxanthine incorporation, we therefore did an in vitro comparison of IC50 values for artemisinin in Plasmodium falciparum-infected erythrocytes from sickle cell trait (AS) and normal (AA) individuals. IC50 values for chloroquine served as control. Without drugs, parasite growth was similar in AA and AS erythrocytes. Gender, age and blood group of donors had no significant effects on parasite growth. IC50 value for artemisinin was 27 ± 14 nM in AS (N = 22) compared to 24 ± 9 nM (N = 27) in AA erythrocytes (P = 0.4). IC50 values for chloroquine were also similar in AA (22 ± 8 nM) and AS (20 ± 11 nM) erythrocytes. These results show no evidence of elevated artemisinin activity on P. falciparum in AS erythrocytes in vitro.
Keywords:P  falciparum  Plasmodium falciparum  Hb  hemoglobin  Hb AA  hemoglobin AA  Hb AS  hemoglobin AS  Hb SS  hemoglobin SS  RBCs  red blood cells  DNA  deoxyribonucleic acid  ACD  acid citrate dextrose  DMSO  dimethyl sulphoxide  _method=retrieve&  _eid=1-s2  0-S0014489408002208&  _mathId=si1  gif&  _pii=S0014489408002208&  _issn=00144894&  _acct=C000054348&  _version=1&  _userid=3837164&  md5=fec96670c845209254f67b168194e667')" style="cursor:pointer  View the MathML source">View the MathML sourcesciencedirect  com/content/image/1-s2  0-S0014489408002208-si1  " target="_blank">gif">  superoxide anoin  [3H]hypoxanthine  2  8-[3H]-hypoxanthine  PfATP6  Plasmodium falciparum calcium-dependent ATPase  SOD  superoxide dismutase  SERCA  sarco/endoplasmic reticulum calcium-dependent ATPases  Artemisinin  CQ  chloroquine  IC50  Malaria
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