THE CHEMOTHERAPY OF RODENT MALARIA .39. ULTRASTRUCTURAL-CHANGES FOLLOWING TREATMENT WITH ARTEMISININE OF PLASMODIUM-BERGHEI INFECTION IN MICE, WITH OBSERVATIONS OF THE LOCALIZATION OF [H-3]-DIHYDROARTEMISININE IN P-FALCIPARUM INVITRO

THE CHEMOTHERAPY OF RODENT MALARIA .39. ULTRASTRUCTURAL-CHANGES FOLLOWING TREATMENT WITH ARTEMISININE OF PLASMODIUM-BERGHEI INFECTION IN MICE, WITH OBSERVATIONS OF THE LOCALIZATION OF [H-3]-DIHYDROARTEMISININE IN P-FALCIPARUM INVITRO
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DOI:
10.1080/00034983.1985.11811933
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发表时间:
1985-01-01
影响因子:
--
通讯作者:
WARHURST, DC
WARHURST, DC
中科院分区:
其他
文献类型:
--
作者:
ELLIS, DS;LI, ZL;WARHURST, DC

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青蒿素(青蒿素)10 mg·kg ~(-1)处理伯氏疟原虫(Plasmodiumberghei)后,其超微结构发生了变化。30分钟后,观察到寄生虫的限制膜和其他膜的变化,以及核糖体组织和内质网的变化。消化泡或色素未见变化,但1小时后核膜起泡,3小时后核质分离。从八小时开始,出现了进一步的退行性变化,包括混乱和死亡。核糖体和内质网的形态学变化与在体外观察到的恶性疟原虫蛋白质合成的抑制在时间上相关。类似地,核质分离的开始与核酸合成抑制的发展相关。氚化还原药物被证明是本地化的寄生虫膜,表明膜完整性的变化可能之前的蛋白质合成的早期抑郁症。青蒿素的膜缔合可能与其两亲性特征和在某些方面与甾醇的相似性有关。
Ultrastructural changes were followed in Plasmodium berghei after the treatment of the mouse host with a single 10 mg kg-1 dose of artemisinine (qinghaosu). After 30 minutes, changes in the limiting and other membranes of the parasite were seen, together with alterations in ribosomal organization and endoplasmic reticulum. No changes were noted in digestive vacuoles or pigment, but nuclear membrane blebbing developed after one hour and segregation of the nucleoplasm after three hours. Further degenerative changes with disorganization and death occurred from eight hours onwards. The morphological changes in ribosomes and endoplasmic reticulum correlate in time with the depression in protein synthesis observed in P. falciparum in vitro. Similarly, the onset of nucleoplasmic segregation correlates with the development of nucleic acid synthesis inhibition. Tritiated reduced drug was shown to be localized in parasite membranes, indicating that changes in membrane integrity might precede the early depression of protein synthesis. Membrane association of artemisinine may be related to its amphipathic characteristics and similarity in some respects to a sterol.