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硫酸葡聚糖对刚地弓形虫急性感染和生长阶段的影响。

Effects of dextran sulfates on the acute infection and growth stages of Toxoplasma gondii.

机构信息

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.

出版信息

Parasitol Res. 2013 Dec;112(12):4169-76. doi: 10.1007/s00436-013-3608-8. Epub 2013 Oct 6.

Abstract

Toxoplasma gondii is one of the most prevalent parasites, causing toxoplasmosis in various warm-blooded animals, including humans. Because of the broad range of hosts susceptible to T. gondii, it had been postulated that a universal component of the host cell surface, such as glycosaminoglycans (GAGs), may act as a receptor for T. gondii infection. Carruthers et al. (Infect Immun 68:4005-4011, 2000) showed that soluble GAGs have also been shown to disrupt parasite binding to human fibroblasts. Therefore, we investigated the inhibitory effect of GAGs and their analogue dextran sulfate (DS) on T. gondii infection. For up to 24 h of incubation after inoculation of T. gondii, the inhibitory effect of GAGs on T. gondii infection and growth inside the host cell was weak. In contrast, DS markedly inhibited T. gondii infection. Moreover, low molecular weight DS particularly slowed the growth of T. gondii inside host cells. DS10 (dextran sulfate MW 10 kDa) was the most effective agent in these in vitro experiments and was therefore tested for its inhibitory effects in animal experiments; infection inhibition by DS10 was confirmed under these in vivo conditions. In this report, we showed that DSs, especially DS10, have the potential of a new type of drug for toxoplasmosis.

摘要

刚地弓形虫是最常见的寄生虫之一,可引起各种温血动物(包括人类)的弓形体病。由于宿主对弓形虫的广泛易感性,有人推测宿主细胞表面的一种通用成分,如糖胺聚糖(GAGs),可能作为弓形虫感染的受体。Carruthers 等人(Infect Immun 68:4005-4011, 2000)表明,可溶性 GAGs 也被证明可破坏寄生虫与人类成纤维细胞的结合。因此,我们研究了 GAGs 及其类似物硫酸葡聚糖(DS)对弓形虫感染的抑制作用。在接种弓形虫后长达 24 小时的孵育过程中,GAGs 对弓形虫感染和宿主细胞内生长的抑制作用较弱。相比之下,DS 显著抑制弓形虫感染。此外,低分子量 DS 特别减缓了宿主细胞内弓形虫的生长。在这些体外实验中,DS10(葡聚糖硫酸盐 MW 10 kDa)是最有效的试剂,因此在动物实验中测试了其抑制作用;在这些体内条件下证实了 DS10 的感染抑制作用。在本报告中,我们表明 DSs,特别是 DS10,具有成为弓形虫病新型药物的潜力。

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