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甲苯咪唑、甲氟喹和硝唑尼特对囊型棘球蚴病的体内和体外疗效

In vivo and in vitro efficacies of mebendazole, mefloquine and nitazoxanide against cyst echinococcosis.

作者信息

Liu Congshan, Zhang Haobing, Yin Jianhai, Hu Wei

机构信息

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory of Parasite and Vector Biology, MOH, WHO Collaborating Centre for Malaria, Schistosomiasis and Filariasis, Shanghai, 200025, China.

出版信息

Parasitol Res. 2015 Jun;114(6):2213-22. doi: 10.1007/s00436-015-4412-4. Epub 2015 Mar 15.

Abstract

Echinococcus granulosus is a cestode parasite. The metacestode stage causes cystic echinococcosis (CE) mainly in the human liver and lung. Current chemotherapy against CE is based on mebendazole and albendazole. However, benzimidazoles result in a low cure rate or are ineffective in many patients; therefore, novel compounds for the treatment of this disease have been studied. Mefloquine was reported to be dramatically effective on cultured Echinococcus multilocularis metacestodes in vitro. And, nitazoxanide has a prominent protoscolicidal effect. However, these compounds have no impact on the growth of cysts harbored in mice. In this study, we investigated the in vitro and in vivo efficacy of mebendazole, mefloquine, and nitazoxanide against E. granulosus protoscoleces, germinal cells, and infected mice. The effect of mebendazole on protoscoleces and germinal cell was proved to be dose-dependent in vitro. And, a reduction of the cyst weight was also the found after oral application of mebendazole to infected mice. Mefloquine (5 and 10 μg/ml) caused death within 24 h of protoscoleces and germinal cells in vitro, whereas a lower concentration of 1 μg/ml was ineffective. In mice infected with E. granulosus, oral mefloquine (200 and 400 mg/kg twice weekly for 2 weeks) showed no reduction in parasite weight. Without affecting the viability of germinal cells and the growth of hydatid cysts, nitazoxanide only showed protoscolicidal effects in infected mice. In conclusion, mebendazole, mefloquine, and nitazoxanide showed various effects on E. granulosus under different conditions. These drugs could be useful to some extent in the treatment of CE.

摘要

细粒棘球绦虫是一种绦虫寄生虫。其幼虫期主要在人体肝脏和肺部引发囊型包虫病(CE)。目前针对CE的化疗药物主要是甲苯咪唑和阿苯达唑。然而,苯并咪唑类药物的治愈率较低,在许多患者中效果不佳;因此,人们一直在研究用于治疗这种疾病的新型化合物。据报道,甲氟喹对体外培养的多房棘球绦虫幼虫具有显著疗效。而且,硝唑尼特具有突出的原头蚴杀灭作用。然而,这些化合物对小鼠体内囊肿的生长没有影响。在本研究中,我们调查了甲苯咪唑、甲氟喹和硝唑尼特对细粒棘球绦虫原头蚴、生发细胞以及感染小鼠的体内外疗效。在体外,甲苯咪唑对原头蚴和生发细胞的作用被证明具有剂量依赖性。而且,给感染小鼠口服甲苯咪唑后,也发现囊肿重量有所减轻。甲氟喹(5和10μg/ml)在体外可使原头蚴和生发细胞在24小时内死亡,而较低浓度的1μg/ml则无效。在感染细粒棘球绦虫的小鼠中,口服甲氟喹(200和400mg/kg,每周两次,共2周)并未使寄生虫重量减轻。在不影响生发细胞活力和包虫囊肿生长的情况下,硝唑尼特仅在感染小鼠中表现出原头蚴杀灭作用。总之,甲苯咪唑、甲氟喹和硝唑尼特在不同条件下对细粒棘球绦虫表现出不同的作用。这些药物在CE的治疗中在一定程度上可能会有帮助。

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