Protective effect of amiodarone in malaria.
According to previous observations, amiodarone triggers suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Eryptosis may in turn accelerate the clearance of Plasmodium-infected erythrocytes. The present study tested whether amiodarone augments phosphatidylserine exposure of Plasmodium-infected erythrocytes, interferes with the development of parasitemia and thus influences the course of malaria. The in vitro infection of human erythrocytes with Plasmodium falciparum (strain BinH) increased annexin V-binding, an effect significantly augmented by amiodarone (10 microM). Amiodarone further significantly decreased intraerythrocytic DNA/RNA content (> or =5 microM) and in vitro parasitemia (> or =1 microM). Following infection of mice with Plasmodiumberghei ANKA by intraperitoneal injection of parasitized murine erythrocytes (1x10(6)) amiodarone (intraperitoneal 50mg/kg b.w.) significantly decreased the parasitemia and increased the survival of P. berghei-infected mice (from 0% to 70% 26 days after infection). Moreover, treatment with amiodarone significantly increased the percentage of PS-exposing infected erythrocytes. In conclusion, amiodarone inhibits intraerythrocytic growth of P. falciparum, enhances suicidal death of infected erythrocytes, decreases parasitemia following P. berghei infection and supports host survival during malaria.
Department of Physiology, University of Tübingen, Gmelinstrasse 5, D-72076 Tübingen, Germany.
Diwakar
D
Bobbala
Ioana
I
Alesutan
Michael
M
Föller
Serena
S
Tschan
Stephan M
SM
Huber
Florian
F
Lang
D000638:Amiodarone / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004912:Erythrocytes / Q000187:drug effects* / Q000469:parasitology; D005260:Female; D006801:Humans; D008288:Malaria / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D051379:Mice; D018512:Parasitemia / Q000097:blood / Q000188:drug therapy; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011956:Receptors, Cell Surface / Q000187:drug effects; D016019:Survival Analysis
D004791:Enzyme Inhibitors; D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor; D000638:Amiodarone