Effect of artemisinin on lipid peroxidation and fluidity of the erythrocyte membrane in malaria.
The effect of artemisinin on membrane fluidity of erythrocytes was investigated using spin labeling compounds, doxyl stearic acids. The membrane fluidity of erythrocytes from the in vitro culture and malaria patients was determined. In vitro, the erythrocytes in parasite culture showed an increase in membrane fluidity which was associated with the parasite counts and stage of parasites. Artemisinin caused reduction in membrane fluidity and the effect was more pronounced in the erythrocytes infected with schizont stage-parasites. In vivo, the elevation of plasma TBARs (thiobarbituric acid reactive substances) and reduction of membrane fluidity were evident in Plasmodium falciparum-infected patients, particularly in severe cases. The levels of plasma TBARs were related to the severity of the disease. Treatment with artemisinin alone showed no effect on plasma TBARs, and did not alter the membrane fluidity. Desferrioxamine, however, reduced oxidative damage during the infection without compromising the therapeutic effect of artemisinin. These findings suggested that the infected erythrocytes were prone to the effect of artemisinin. Addition of a chelator such as desferrioxamine is beneficial and can improve the treatment of severe malaria.
Sibmooh
N
N
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand. scnsm@mahidol.ac.th
Pipitaporn
B
B
Wilairatana
P
P
Dangdoungjai
J
J
Udomsangpetch
R
R
Looareesuiwan
S
S
Chantharaksri
U
U
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004311:Double-Blind Method; D004910:Erythrocyte Membrane / Q000187:drug effects*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008288:Malaria / Q000097:blood*; D016778:Malaria, Falciparum / Q000097:blood; D008560:Membrane Fluidity / Q000187:drug effects*; D010963:Plasmodium falciparum; D012717:Sesquiterpenes / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000962:Antimalarials; D037621:Artemisinins; D003497:Cyclic N-Oxides; D012717:Sesquiterpenes; D017392:Thiobarbituric Acid Reactive Substances; C037404:12-doxylstearic acid; D000077332:Artesunate; C031327:artemisinin; D003676:Deferoxamine