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学科主题: 生命有机化学
题名: Schistosoma japonicum: in vitro effects of artemether combined with haemin depend on cultivation media and appraisal of artemether products appearting in the media
其他题名: 蒿甲醚和血红素抗日本血吸虫效果对培养基的依赖性以及培养基质中蒿甲醚产物的鉴定
作者: Xiao SH(肖树华) ; Wu YL(吴毓林) ; Marcel Tanner ; Wu WM(吴文敏) ; Jurg Utzinger ; Jin-Yan Mei ; Bernard Scorneaux ; Jacques Chollet ; Zhai ZL(翟自立)
刊名: Parasitol. Res.
发表日期: 2003-01-01T00:00:00Z
卷: 89, 期:6, 页:459-466
收录类别: SCI
部门归属: 中国科学院上海有机化学研究所生命有机国家重点实验室; Swiss Tropical Institute; Office of Populaion Research, Princeton Univerity
英文摘要: We recenly found that the exposnre of schistosomes in viuo to aremether plus haemin can lead to parasite death, while exposure to each compound singly had no effect. Since these observations might be relevant to understanding the mechanism of action of artemether against schistosomes, we conducted additional experiments. First, we performed a comparative appraisal of Schistosoma japonicum surival after incubation in two media, namely Hanks' balanced salt solution (HBSS) and RPMI 1640, snpplemented with inactivated alf serum,antibiotics and different concetrations of aremether and/or haemin. Worm mortalities were consistenly higher and occurrecd faster in HBSS when compared to RPMI 1640. Second, we investigated the ehaviour of artemether in different chmlical systems, including re-duced glutathione or cysteine, in the presence ofhamin or ferrous- sulfate. Cleavage of the endoperoxide bridge of artemether occurred in an xperiments, consistentlyone has not been described previously. Third, RPMI l640 and HBSS media were suoolemented with artemether and haemin in the presence of S.japonicun. The consumption of artemether in RPMI 1640 was much faster than in HBSS. Trace amouns of artemether and five free radical reaction products of artemether ould be detected in RPMI 1640 after 24-48 h. In contrast, large amounts of arternether remained without the ormation of free radical Products in HBSS under the same conditions. These findings coincide with ignificantly higher schistosome mortalities employing HBSS instead of RPMI 1640. Our results suggest that it is artemether or an active metabolite thereof (most likely a carbon-centred free radical), rather than any free radical reaction product that is harmful for the worms. We speculate that schistosomes ingest artemether and cleave it in their gut. This cleavage is induced by haemin or another iron-containing olecule.These findings might be a further step forward in elucidating the mechanism of action of rtemether against schistosomes.
语种: 英语
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/14058
Appears in Collections:生命有机化学国家重点实验室_期刊论文

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Recommended Citation:
Xiao SH,Wu YL,Marcel Tanner,et al. Schistosoma japonicum: in vitro effects of artemether combined with haemin depend on cultivation media and appraisal of artemether products appearting in the media[J]. Parasitol. Res.,2003,89(6):459-466.
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