Journal ArticleDOI
Glutathione--functions and metabolism in the malarial parasite Plasmodium falciparum.
TLDR
Methylene blue, an inhibitor of the structurally known P. falciparum glutathione reductase, appears to be a promising antimalarial medication when given in combination with chloroquine.Abstract:
When present as a trophozoite in human erythrocytes, the malarial parasite Plasmodium falciparum exhibits an intense glutathione metabolism. Glutathione plays a role not only in antioxidative defense and in maintaining the reducing environment of the cytosol. Many of the known glutathione-dependent processes are directly related to the specific lifestyle of the parasite. Reduced glutathione (GSH) supports rapid cell growth by providing electrons for deoxyribonucleotide synthesis and it takes part in detoxifying heme, a product of hemoglobin digestion. Free radicals generated in the parasite can be scavenged in reaction sequences involving the thiyl radical GS . as well as the thiolate GS-. As a substrate of glutathione S-transferase, glutathione is conjugated to nondegradable compounds including antimalarial drugs. Furthermore, it is the coenzyme of the glyoxalase system which detoxifies methylglyoxal, a byproduct of the intense glycolysis taking place in the trophozoite. Proteins involved in GSH-dependent processes include glutathione reductase, glutaredoxins, glyoxalase I and II, glutathione S-transferases, and thioredoxins. These proteins, as well as the ATP-dependent enzymes of glutathione synthesis, are studied as factors in the pathophysiology of malaria but also as potential drug targets. Methylene blue, an inhibitor of the structurally known P. falciparum glutathione reductase, appears to be a promising antimalarial medication when given in combination with chloroquine.read more
Citations
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Journal ArticleDOI
Oxidative stress in malaria parasite-infected erythrocytes: Host-parasite interactions
Katja Becker,Leann Tilley,Jonathan L. Vennerstrom,David L. Roberts,Stephen J. Rogerson,Hagai Ginsburg +5 more
TL;DR: The presently available knowledge on sources and detoxification pathways of reactive oxygen species in malaria parasite-infected red cells, on clinical aspects of redox metabolism and redox-related mechanisms of drug action as well as future prospects for drug development is summarized.
Journal ArticleDOI
Redox and antioxidant systems of the malaria parasite Plasmodium falciparum
TL;DR: In addition to these cytosolic redox systems the parasite also has an important mitochondrial antioxidant defence system and it is suggested that lipoic acid plays a pivotal part in defending the organelle from oxidative damage.
Journal ArticleDOI
Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia.
TL;DR: Inhibitors of antioxidant enzymes such as trypanothione reductase are, indeed, parasiticidal but they can also delay or prevent resistance against a number of other antiparasitic drugs.
Journal ArticleDOI
Next-Generation Antimalarial Drugs: Hybrid Molecules as a New Strategy in Drug Design.
Francis W. Muregi,Akira Ishih +1 more
TL;DR: This review is focused on several hybrid molecules that have been developed, with particular emphasis on those deemed to have high potential for development for clinical use.
Journal ArticleDOI
Methylene blue as an antimalarial agent.
R. Heiner Schirmer,Boubacar Coulibaly,August Stich,Michael Scheiwein,Heiko Merkle,Jana Eubel,Katja Becker,Heiko Becher,Olaf Müller,Thomas Zich,Wolfgang Schiek,Bocar Kouyaté +11 more
TL;DR: The combination of chloroquine with methylene blue (BlueCQ) is studied as a possible medication for malaria in endemic regions and a pilot study with glucose-6-phosphate dehydrogenase-sufficient adult patients has been conducted recently.
References
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