Effects of malaria heme products on red blood cell deformability.
In falciparum malaria, the deformability of the entire erythrocyte population is reduced in proportion to disease severity, and this compromises microcirculatory blood flow through vessels partially obstructed by cytoadherent parasitized erythrocytes. The cause of rigidity of uninfected erythrocytes in not known but could be mediated by malaria heme products. In this study, we show that red blood cell deformability (RBC-D), measured by laser-assisted optical rotational cell analyzer, decreased in a dose-dependent manner after incubation with hemin and hydrogen peroxide but not with hemoglobin or beta-hematin. Hemin also reduced mean red cell volume. Albumin decreased and N-acetylcysteine (NAC) both prevented and reversed rigidity induced by hemin. Hemin-induced oxidative damage of the membrane seems to be a more important contributor to pathology than cell shrinkage because the antioxidant NAC restored RBC-D but not red blood cell volume. The findings suggest novel approaches to the treatment of potentially lethal malaria.
Nuchsongsin
Forradee
F
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Chotivanich
Kesinee
K
Charunwatthana
Prakaykaew
P
Omodeo-Salè
Fausta
F
Fausta
Omodeo-Salè
OS
Taramelli
Donatella
D
Day
Nicholas P
NP
White
Nicholas J
NJ
Dondorp
Arjen M
AM
D000111:Acetylcysteine / Q000494:pharmacology; D000418:Albumins / Q000378:metabolism / Q000494:pharmacology*; D000740:Anemia / Q000097:blood / Q000469:parasitology; D000975:Antioxidants / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects* / Q000469:parasitology* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006420:Hemeproteins / Q000378:metabolism / Q000494:pharmacology*; D006427:Hemin / Q000378:metabolism / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000097:blood*
D000418:Albumins; D000975:Antioxidants; D006420:Hemeproteins; D006454:Hemoglobins; C020753:hemozoin; D006427:Hemin; D006861:Hydrogen Peroxide; D005978:Glutathione; D000111:Acetylcysteine