Hepatic metabolism of artemisinin drugs--III. Induction of hydrogen peroxide production in rat liver microsomes by artemisinin drugs.
1. In this communication, induction of hydrogen peroxide production by the semisynthetic antimalarial drugs of the artemisinin class (beta-arteether, beta-artelinic acid and dihydroartemisinin) in rat liver microsomes, is reported. 2. Endogenous, NADPH-dependent, production of hydrogen peroxide in rat liver microsomes was enhanced in the presence of arteether and artelinic acid, but not in the presence of dihydroartemisinin. 3. NADPH-dependent metabolism of arteether and artelinic acid was closely coupled to the drug-induced production of hydrogen peroxide. 4. The redox cycle of cytochrome P-450 was presented, which describes satisfactorily both the endogenous and the drug-assisted hydrogen peroxide production in rat liver microsomes; also, the rate-limiting step of the cycle was identified.
Walter Reed Army Institute of Research, Division of Experimental Therapeutics, Washington, D.C. 20307.
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D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000378:metabolism / Q000494:pharmacology*
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C062768:artelinic acid; D009249:NADP; C039060:artenimol; C031327:artemisinin; D006861:Hydrogen Peroxide; C055141:artemotil