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硝唑尼特和氟苯达唑联合作用诱导猪囊尾蚴体外代谢应激。

In vitro metabolic stress induced by nitazoxanide and flubendazole combination in Taenia crassiceps cysticerci.

机构信息

Laboratory of Studies of the Host-parasite Relationship, Tropical Pathology and Public Health Institute, Federal University of Goias, Brazil.

Laboratory of Studies of the Host-parasite Relationship, Tropical Pathology and Public Health Institute, Federal University of Goias, Brazil.

出版信息

Exp Parasitol. 2022 Jul;238:108265. doi: 10.1016/j.exppara.2022.108265. Epub 2022 May 5.

DOI:10.1016/j.exppara.2022.108265
PMID:35525309
Abstract

Taenia crassiceps is often used as experimental model for T. solium cysticercosis studies. Currently cysticercosis antiparasitic treatment is based on albendazole and praziquantel which may present side effects and parasitic resistance. The search for other antiparasitic drugs is necessary. Nitazoxanide (NTZ) and flubendazole (FLB) are broad spectrum antiparasitic drugs that present anti-cysticercosis effect. Metabolic analyses help to determine the impact of these drugs on parasites. The aim of this study was to determine the impact on the production and excretion of organic metabolites in T. crassiceps cysticerci after in vitro exposure to NTZ and FLB, isolated or in combination. T. crassiceps cysticerci were culture in RPMI medium and exposed to 10 μg/mL of NTZ, 10 μg/mL of FLB or 10 μg/mL of NTZ +10 μg/mL of FLB. 24 h after exposure, the parasites were chromatographic analyzed to determine the impact of these drugs on glycolysis, homolactic fermentation, tricarboxylic acid cycle, fatty acids oxidation and proteins catabolism. It was possible to determine that the drugs combination induced greater metabolic impact on cysticerci in comparison to the isolated drugs exposure. The drugs combination induced gluconeogenesis, metabolic acidosis, increase in tricarboxylic acid cycle and in proteins catabolism. While the NTZ isolated exposure induced metabolic acidosis and protein catabolism and the FLB isolate exposure induced gluconeogenesis and protein catabolism. These results show that the combination of drugs with different modes of action increase the antiparasitic effect and may be indicated as alternative cysticercosis treatments.

摘要

多头蚴绦虫常被用作猪囊尾蚴研究的实验模型。目前,囊尾蚴病的驱虫治疗主要基于阿苯达唑和吡喹酮,它们可能会产生副作用和寄生虫耐药性。因此,有必要寻找其他驱虫药物。硝唑尼特(NTZ)和氟苯达唑(FLB)是具有广谱抗寄生虫作用的药物,具有抗囊尾蚴作用。代谢分析有助于确定这些药物对寄生虫的影响。本研究旨在确定硝唑尼特和氟苯达唑单独或联合体外暴露后对多头蚴囊尾蚴有机代谢产物的产生和排泄的影响。将多头蚴囊尾蚴在 RPMI 培养基中培养,并暴露于 10μg/mL 的硝唑尼特、10μg/mL 的氟苯达唑或 10μg/mL 的硝唑尼特+10μg/mL 的氟苯达唑中。暴露 24 小时后,对寄生虫进行色谱分析,以确定这些药物对糖酵解、同型乳酸发酵、三羧酸循环、脂肪酸氧化和蛋白质分解代谢的影响。结果表明,与单独使用药物相比,药物联合使用对囊尾蚴的代谢影响更大。药物联合使用诱导了糖异生、代谢性酸中毒、三羧酸循环增加和蛋白质分解代谢增加。而单独使用硝唑尼特诱导了代谢性酸中毒和蛋白质分解代谢,单独使用氟苯达唑诱导了糖异生和蛋白质分解代谢。这些结果表明,具有不同作用机制的药物联合使用可以增加驱虫效果,可能作为囊尾蚴病的替代治疗方法。

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