青蒿琥酯及四种经典抗疟药对大鼠肝线粒体亚铁螯合酶活性的影响

Effects of artesunate and four classical antimalarials on mito chondrial ferrochelatase activity in isolated rat liver

青蒿琥酯及四种经典抗疟药对大鼠肝线粒体亚铁螯合酶活性的影响姚朗１石笑春滕翕和熊春生（军事医学科学院微生物流行病研究所，北京１０００７１）青蒿琥酯（ａｒｔｅｓｕｎａｔｅ，Ａｒｔ）为新型抗疟药青蒿素衍生物，临床前毒理研究发现Ａｒｔ可引起外周血网织红细胞减...

The effects of artesunate(Art) and four classical antimalarials on the mitochondrial ferrochelatase(FC) activity in isolated rat liver were studied with pyridine hemochromogen method. It was shown that Art markedly inhibited the FC activity whether ferrous or ferric ion was used as substrate, but the heme biosynthesis from ferric ion was more susceptible to Art. The IC 50 of Art on FC was 165 μmol·L -1 for Fe 2+ and 30.2 μmol·L -1 for Fe 3+ substrate, respectively. It meant that Art not only inhibited the FC activity directly, but also interfered with Fe 3+ reduction and/or utilization by mitochondria. So that Art could produce stronger inhibitory effect on heme biosynthesis, and the effect might be one of the toxic mechanisms of Art on erythropoiesis. The inhibition of FC activity was not found with 1 mmol·L -1 chlo roquine, quinine, cyclochloroguanide or primaquine treatment.