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阿苯达唑联合百里酚对多房棘球绦虫原头节和中绦期幼虫的疗效。

Efficacy of albendazole in combination with thymol against Echinococcus multilocularis protoscoleces and metacestodes.

作者信息

María Albani Clara, Celina Elissondo María

机构信息

Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, 7600 Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.

Laboratorio de Zoonosis Parasitarias, Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3350, 7600 Mar del Plata, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.

出版信息

Acta Trop. 2014 Dec;140:61-7. doi: 10.1016/j.actatropica.2014.08.007. Epub 2014 Aug 19.

DOI:10.1016/j.actatropica.2014.08.007
PMID:25149355
Abstract

The larval (metacestode) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), a mainly hepatic disease characterized by continuous asexual proliferation of metacestodes by exogenous budding, resulting in the tumor-like, infiltrative growth of the parasite lesion. Current chemotherapeutical treatment of AE relies on the use of benzimidazoles, albendazole (ABZ) and mebendazole, but these drugs act parasitostatic rather than parasitocidal, and due to their low success rate they imply a lifelong application causing severe side effects. Thymol is one of the major components of the essential oils of Thymus and is a widely known anti-microbial agent. The aim of the present work was to compare the efficacy of albendazole (ABZ) and thymol separately or combined on E. multilocularis protoscoleces and metacestodes. For this purpose, microscopical examinations at different time points were carried out. Moreover the tegumentary enzyme gamma glutamyl transferase (GGT) was measured to quantify the damage in metacestodes. Even though treatments of in vitro cultured E. multilocularis protoscoleces or metacestodes with ABZ or/and thymol showed that the drugs have an adverse effect on parasite viability, the combination of the two compounds at the concentration of 10μg/ml showed the maximum anti-parasitic effect. Three days postincubation the first effects of the treatment were detected on protoscoleces and a marked reduction in viability (33%) was registered at day 18. Incubation of E. multilocularis metacestodes in the presence of ABZ 10μg/ml+thymol 10μg/ml during 10 days resulted in dramatic alterations such as strongly irregular and fissured surface and markedly disrupted vesicles. Scanning electron microscopy showed that protoscoleces as well as the germinal layer of E. multilocularis metacestodes were dramatically damaged following ABZ or/and thymol treatment. Also an important increase of tegumentary enzyme GGT was registered after 72h postincubation with both drugs. The data reported in this article demonstrate a clear in vitro effect of ABZ+thymol against E. multilocularis protoscoleces and metacestodes.

摘要

多房棘球绦虫的幼虫(中绦期)可引发泡型包虫病(AE),这是一种主要累及肝脏的疾病,其特征为中绦期通过外生性出芽进行持续无性增殖,导致寄生虫病灶呈肿瘤样浸润性生长。目前AE的化疗依赖于使用苯并咪唑类药物,如阿苯达唑(ABZ)和甲苯达唑,但这些药物仅具有抑制寄生虫生长的作用而非杀灭作用,且由于其成功率较低,意味着需要终身用药,还会引发严重的副作用。百里香酚是百里香属植物精油的主要成分之一,是一种广为人知的抗菌剂。本研究的目的是比较阿苯达唑(ABZ)和百里香酚单独使用或联合使用对多房棘球绦虫原头节和中绦期的疗效。为此,在不同时间点进行了显微镜检查。此外,还检测了体表酶γ-谷氨酰转移酶(GGT),以量化中绦期的损伤情况。尽管用ABZ或/和百里香酚处理体外培养的多房棘球绦虫原头节或中绦期显示这些药物对寄生虫活力有不良影响,但两种化合物以10μg/ml的浓度联合使用时显示出最大的抗寄生虫效果。孵育三天后,在原头节上检测到治疗的初步效果,在第18天记录到活力显著降低(33%)。在10μg/ml ABZ + 10μg/ml百里香酚存在的情况下,将多房棘球绦虫中绦期孵育10天,会导致显著变化,如表面强烈不规则且有裂缝,囊泡明显破裂。扫描电子显微镜显示,ABZ或/和百里香酚处理后,多房棘球绦虫原头节以及中绦期的生发层均受到严重损伤。与两种药物孵育72小时后,体表酶GGT也有显著升高。本文报道的数据表明,ABZ + 百里香酚在体外对多房棘球绦虫原头节和中绦期有明显作用。

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