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腹腔内和颅内实验性囊虫病在用阿苯达唑和硝唑尼特单独或联合治疗后表现出不同的代谢偏好。

Intraperitoneal and intracranial experimental cysticercosis present different metabolic preferences after treatment with isolated or combined albendazole and nitazoxanide.

机构信息

Laboratory of studies of the host-parasite relationship, Tropical Pathology and Public Health Institute, Federal University of Goias, Rua 235, s/n, Setor Universitário, Goiania, Goias CEP 74605-050 Brazil.

Laboratory of studies of the host-parasite relationship, Tropical Pathology and Public Health Institute, Federal University of Goias, Rua 235, s/n, Setor Universitário, Goiania, Goias CEP 74605-050 Brazil.

出版信息

Acta Trop. 2022 Feb;226:106264. doi: 10.1016/j.actatropica.2021.106264. Epub 2021 Dec 14.

Abstract

Cysticercosis is a zoonotic public health issue especially severe when the parasite is in the central nervous system although it may be found all over the human organism. Taenia crassiceps cysticerci inoculated in mice is the experimental model used to study cysticercosis. The most used cysticercosis treatment is with albendazole (ABZ). Nitazoxanide (NTZ) has been experimentally tested against this parasite. Metabolic analysis has been used to determine drugs impact on the parasite. The aim of this study was to determine the in vivo metabolic impact of the ABZ-NTZ combination in T. crassiceps cysticerci inoculated in mice peritoneal and intracranial cavities. Mice were experimentally inoculated with T. crassiceps cysticerci in the intraperitoneal cavity or in the intracranial one. Thirty days after the infection they were treated with NaCl 0.9% (control group), 50 mg/kg of ABZ, 50 mg/kg of NTZ or 50 mg/kg of NTZ and ABZ (ABZ/NTZ combination). 24 h after treatment the animals were euthanized and the cysticerci analyzed through high performance chromatography and spectrophotometry in order to detect the glycolytic, mitochondrial and protein catabolism pathways. The intracranial parasites used more intensely the homolactic fermentation while the intraperitoneal ones presented a greater use of the mitochondrial pathways and protein catabolism. Regarding the glycolytic pathways, it was possible to observe a significant impact induced by the drugs used, both isolated or in combination. It was possible to detect an increase in the fumarate reductase pathway after the drugs exposure and no impact in the protein's catabolism. Therefore, the cysticerci showed different uses of metabolic pathways regarding the site of inoculation due to the availability of nutrients inherent of each environment. This study showed the parasite metabolic resilience and capability of use of different biochemical pathways in order to ensure survival in spite of a hostile environment.

摘要

囊虫病是一种人畜共患的公共卫生问题,尤其是当寄生虫存在于中枢神经系统时,尽管它可能存在于人体的各个部位。接种在小鼠体内的猪囊尾蚴是研究囊虫病的实验模型。最常用的囊虫病治疗方法是使用阿苯达唑(ABZ)。硝唑尼特(NTZ)已在实验中针对这种寄生虫进行了测试。代谢分析已被用于确定药物对寄生虫的影响。本研究旨在确定 ABZ-NTZ 联合用药对接种在小鼠腹腔和颅内的猪囊尾蚴的体内代谢影响。小鼠通过腹腔或颅内接种猪带绦虫囊尾蚴进行实验性感染。感染 30 天后,用 0.9%NaCl(对照组)、50mg/kgABZ、50mg/kgNTZ 或 50mg/kgNTZ 和 ABZ(ABZ/NTZ 联合用药)对其进行治疗。治疗 24 小时后,处死动物并通过高效液相色谱和分光光度法分析囊尾蚴,以检测糖酵解、线粒体和蛋白质分解代谢途径。颅内寄生虫更强烈地利用同型乳酸发酵,而腹腔内寄生虫则表现出更大程度地利用线粒体途径和蛋白质分解代谢。关于糖酵解途径,观察到单独或联合使用药物会产生显著影响。药物暴露后发现延胡索酸还原酶途径增加,而蛋白质分解代谢没有影响。因此,由于每种环境中固有营养物质的可用性,接种部位不同的囊尾蚴显示出对代谢途径的不同利用。本研究表明寄生虫具有代谢弹性和利用不同生化途径的能力,以确保在恶劣环境中生存。

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