Hemozoin chloroquine

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  1. yanpoltava New Member

    Hemozoin chloroquine


    These hematophagous organisms such as Malaria parasites (Plasmodium spp.), Rhodnius and Schistosoma digest haemoglobin and release high quantities of free heme, which is the non-protein component of hemoglobin. Heme is a prosthetic group consisting of an iron atom contained in the center of a heterocyclic porphyrin ring.

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    Chloroquine resistant P. berghei hemozoin crystals are morphologically smaller but similar to those formed by chloroquine sensitive parasites. Chloroquine resistance in P. vivax is distinct from P. berghei even though both infect reticulocytes. The major action of chloroquine is to inhibit the formation of hemozoin Hz from the heme released by the digestion of hemoglobin Hb. The free heme then lyses membranes and leads to parasite death. Chloroquine resistance is due to a decreased accumulation of chloroquine in the food vacuole. Chloroquine acts by forming toxic complexes with heme molecules and interfering with their crystallization. 381 This mechanism of action explains why chloroquine is effective against developing intraerythrocytic trophozoites but ineffective against other parasite stages i.e. mature gametocytes, liver schizonts that do not actively consume hemoglobin.

    In malaria parasites, hemozoin is often called malaria pigment. Free heme is toxic to cells, so the parasites convert it into an insoluble crystalline form called hemozoin.

    Hemozoin chloroquine

    Replication of Plasmodium in reticulocytes can occur without., Mechanisms of drug action and resistance

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  3. Hemozoin collects in the digestive vacuole as insoluble crystals. Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Chloroquine then becomes protonated to CQ2+, as the digestive vacuole is known to be acidic pH 4.7; chloroquine then cannot leave by diffusion.

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    Chloroquine is thought to exert its antimalarial effect by preventing the polymerization of toxic heme released during proteolysis of hemoglobin in the Plasmodium digestive vacuole. The mechanism of this blockade has not been established. Aug 10, 2013 In the infected erythrocyte the malaria parasite generates large quantities of toxic heme which it has to render innocuous by polymerizing it into hemozoin. The mechanism of quinine and all its derivates, chloroquine, amodiaquine operates by inhibiting this hemozoin crystallization. The general accepted conclusion is that chloroquine interferes with the process in which heme is converted to hemozoin 10. Chloroquine concentrates in the food vacuole up to 1000-fold. Chloroquine, exists in unprotonated form, CQ, monoprotonated form, CQ + and diprotonated form, CQ ++ form 13. Unprotonated form of chloroquine is membrane permeable and it freely diffuses into the red blood cell.

     
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