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苯并咪唑衍生物治疗实验性神经囊尾蚴病后主要能量途径的部分抑制及其代谢后果。

Partial inhibition of the main energetic pathways and its metabolic consequences after treatment with benzimidazole derivatives in experimental neurocysticercosis.

机构信息

Tropical Pathology and Public Health Institute, Federal University of Goias, Goiania, Brazil.

Chemistry Faculty, National Autonomous University of Mexico, Mexico City, Mexico.

出版信息

Parasitology. 2019 Oct;146(12):1578-1582. doi: 10.1017/S0031182019000933. Epub 2019 Jul 31.

Abstract

Benzimidazole derivatives such as albendazole (ABZ) and mebendazole are important molecules used in helminthic treatment. Neurocysticercosis is the main cause of acquired epilepsy throughout the world and is currently treated with ABZ. New molecules have been studied in order to aid in the treatment of this neglected tropical disease, among them RCB15 and RCB20. The aim of this study was to evaluate the metabolic impact of RCB15 and RCB20 on Taenia crassiceps cysticerci intracranially inoculated in Balb/c mice. Thirty days after the inoculation the mice were treated with 50 mg kg-1 of RCB15, RCB20, ABZ or NaCl 0.9%. The euthanasia and cysticerci removal were performed 24 h after the treatment. The cysticerci were analysed through high performance liquid chromatography. After the treatments, there was an impairment in the main energetic pathways such as glycolytic pathway, homolactic fermentation or in mitochondrion energy production detected through the decrease in pyruvate, lactate, oxaloacetate, malate and fumarate concentrations. This induced the parasite to resort to alternative energetic pathways such as proteins catabolism, propionate fermentation and fatty acids oxidation. Therefore, benzimidazole derivatives are a promising alternative to ABZ use as they also reach the brain tissue and induce a metabolic stress in the cysticerci.

摘要

苯并咪唑衍生物,如阿苯达唑(ABZ)和甲苯达唑,是治疗蠕虫病的重要分子。神经囊尾蚴病是全世界获得性癫痫的主要原因,目前用 ABZ 治疗。为了帮助治疗这种被忽视的热带病,已经研究了新的分子,其中包括 RCB15 和 RCB20。本研究旨在评估 RCB15 和 RCB20 对颅内接种 Taenia crassiceps 囊尾蚴的 Balb/c 小鼠的代谢影响。接种后 30 天,用 50mgkg-1 的 RCB15、RCB20、ABZ 或 NaCl 0.9%治疗小鼠。治疗后 24 小时处死小鼠并取出囊尾蚴。通过高效液相色谱法分析囊尾蚴。治疗后,通过检测丙酮酸、乳酸、草酰乙酸、苹果酸和富马酸浓度的降低,发现糖酵解途径、同型乳酸发酵或线粒体能量产生等主要能量途径受到损害。这促使寄生虫利用替代的能量途径,如蛋白质分解、丙酸发酵和脂肪酸氧化。因此,苯并咪唑衍生物是 ABZ 的有前途的替代品,因为它们也能到达脑组织并在囊尾蚴中引起代谢应激。

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