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硒诱导恶性疟原虫发生凋亡样细胞死亡。

Selenium-induced apoptosis-like cell death in Plasmodium falciparum.

作者信息

Suradji Eka W, Hatabu Toshimitsu, Kobayashi Kenji, Yamazaki Chiho, Abdulah Rizky, Nakazawa Minato, Nakajima-Shimada Junko, Koyama Hiroshi

机构信息

Department of Public Health, Gunma University, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.

Gunma University Graduate School of Health Sciences, 3-39-15 Showa-machi, Maebashi 371-8514, Japan.

出版信息

Parasitology. 2011 Dec;138(14):1852-62. doi: 10.1017/S0031182011001399. Epub 2011 Aug 19.

Abstract

Plasmodium falciparum has for some time been developing resistance against known anti-malarial drugs, and therefore a new drug is urgently needed. Selenium (Se), an essential trace element, in the form of inorganic Se, selenite (SeO32-), has been reported to have an anti-plasmodial effect, but its mechanism is still unclear. In the present study, we evaluated the anti-plasmodial effect of several Se compounds against P. falciparum in vitro. The anti-plasmodial effect of several Se compounds was analysed and their apoptosis-inducing activity was evaluated by morphological observation, DNA fragmentation assay and mitochondrial function analysis. SeO32-, methylseleninic acid, selenomethionine and selenocystine have anti-plasmodial effects with 50% inhibition concentration at 9, 10, 45, and 65 μm, respectively, while selenate and methylselenocysteine up to 100 μm have no effect on parasite growth. The effective Se compounds caused the parasites to become shrunken and pyknotic and significantly increased mitochondrial damage against P. falciparum compared to the untreated control. In conclusion, SeO32-, methylseleninic acid, selenomethionine and selenocystine have anti-plasmodial activities that induce apoptosis-like cell death in P. falciparum, and the anti-plasmodial effects of Se seem to be based on its chemical forms. The apoptosis-like cell-death mechanism in P. falciparum can be beneficial to respond to the growing problem of drug resistance.

摘要

恶性疟原虫对已知抗疟药物产生耐药性已有一段时间,因此迫切需要一种新药。硒(Se)作为一种必需的微量元素,以无机硒亚硒酸盐(SeO32-)的形式存在,据报道具有抗疟原虫作用,但其机制仍不清楚。在本研究中,我们评估了几种硒化合物在体外对恶性疟原虫的抗疟作用。分析了几种硒化合物的抗疟作用,并通过形态学观察、DNA片段化分析和线粒体功能分析评估了它们的凋亡诱导活性。亚硒酸盐、甲基亚硒酸、硒代蛋氨酸和硒代胱氨酸具有抗疟作用,其50%抑制浓度分别为9、10、45和65μm,而高达100μm的硒酸盐和甲基硒代半胱氨酸对疟原虫生长没有影响。与未处理的对照相比,有效的硒化合物使疟原虫萎缩并固缩,并显著增加了对恶性疟原虫的线粒体损伤。总之,亚硒酸盐、甲基亚硒酸、硒代蛋氨酸和硒代胱氨酸具有抗疟活性,可诱导恶性疟原虫发生类似凋亡的细胞死亡,硒的抗疟作用似乎基于其化学形式。恶性疟原虫中类似凋亡的细胞死亡机制可能有助于应对日益严重的耐药问题。

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