HEPATIC-METABOLISM OF ARTEMISININ DRUGS .3. INDUCTION OF HYDROGEN-PEROXIDE PRODUCTION IN RAT-LIVER MICROSOMES BY ARTEMISININ DRUGS

被引:7
作者
LESKOVAC, V [1 ]
PEGGINS, JO [1 ]
机构
[1] WALTER REED ARMY MED CTR, DIV EXPTL THERAPEUT, WASHINGTON, DC 20307 USA
来源
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY | 1992年 / 101卷 / 02期
关键词
D O I
10.1016/0742-8413(92)90261-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:203 / 208
页数:6
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