Hemin Lyses Malaria Parasites

Abstract

Malaria parasites isolated from mouse erythrocytes are lysed by ferriprotoporphyrin IX chloride (hemin) or by a chloroquine-hemin complex in amounts that could be produced by release of less than 0.1 percent of the heme in erythrocytic hemoglobin. This effect of hemin may explain the protection against malaria provided by thalassemia and other conditions causing intracellular denaturation of hemoglobin. The toxicity of the chloroquine-hemin complex may explain the selective antimalarial action of chloroquine.

A central role for free heme in the pathogenesis of severe malaria: the missing link?

“…Hb degradation, however, generates free heme and reactive oxygen species (ROS), the combination of which is highly deleterious to erythrocytic schizonts [22] as well as to the infected host.…”

“…Under homeostatic conditions, ferric HbFe 3+ (αβ) is scavenged by haptoglobin (Hp). The very high affinity of Hp towards Hb (>10 10 mol −1 in humans) is sustained by two Hp-binding sites in the Hb β chain, i.e., β [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] and β 131-146 and one in the α chain, i.e., α 121-l27 [94]. Binding of Hp to Hb also stabilizes heme, inhibiting its release [95].…”

Interactions of hemin, antimalarial drugs and hemin-antimalarial complexes with phospholipid monolayers

“…Hemin can cause lysis of mouse [1,2] and human erythrocytes [3] and of malaria parasites [4,5]. Other types of cells were demonstrably resistant to this lytic effect (see Ref.…”

Quinolines block every step of malaria heme crystal growth

“…Cohen et al first observed quinoline-heme complexes that were postulated to be toxic to the malaria parasites (7). Subsequent work demonstrated quinolone-heme complex interference with Plasmodium enzymes and insertion into membranes (8). However, this substrate hypothesis was not able to explain why many quinoline drugs that bind heme were unable to kill the malaria parasite.…”