title: Evidence that haem iron in the malaria parasite is not needed for the antimalarial effects of artemisinin.
abstract: The role of haem iron (II) and oxidative stress in the activation and antimalarial activity of artemisinin is unclear. Thus, we submitted malaria parasite to modified culture conditions: artemisinin activity increased by 20-30% under an oxygen-rich atmosphere (20% O2 instead of "standard" 1% O2), and by 40-50% in the presence of carboxy-haemoglobin, and 2% carbon monoxide, conditions which inhibit haem iron (II) reactivity. In all cases, parasite growth and chloroquine activity were unaffected. We conclude that in the malaria parasite artemisinin is not activated by haem iron and that free radicals are not needed for its toxicity.
authors.affiliation: Istituto di Microbiologia, Universita' di Milano, Via Pascal 36, 20133 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Parapini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Basilico
authors.forename: Monica
authors.initials: M
authors.lastname: Mondani
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
authors.forename: Donatella
authors.initials: D
authors.lastname: Taramelli
authors.forename: Diego
authors.initials: D
authors.lastname: Monti
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000737:chemistry / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism / Q000469:parasitology; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D008288:Malaria / Q000469:parasitology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D006454:Hemoglobins; D012717:Sesquiterpenes; D006418:Heme; D002248:Carbon Monoxide; D002738:Chloroquine; C031327:artemisinin; D007501:Iron; D010100:Oxygen