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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
Affiliation: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     stixSupport"   id="  mmlsi1"  >  inlMMLBox"  >  submitCitation('/science?_ob=MathURL&  _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  "  >  19"   border="  0"   style="  vertical-align:bottom"   width="  22"   alt="  View the MathML source"   title="  View the MathML source"   src="  http://binary-services.sciencedirect.com/content/image/1-s2.0-S0014489408002208-si1.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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