McConville M, Brennan G P, McCoy M, Castillo R, Hernandez-Campos A, Ibarra F, Fairweather I
Parasite Proteomics and Therapeutics Research Group, School of Biological Sciences, Queens University Belfast, Medical Biology Centre, Belfast, Northern Ireland.
Parasitology. 2006 Aug;133(Pt 2):195-208. doi: 10.1017/S0031182006000114. Epub 2006 May 2.
Mature Fasciola hepatica of the triclabendazole-resistant Sligo isolate were incubated in vitro with 10 microg/ml of the sulphoxide metabolite of compound alpha [5-chloro-2-methylthio-6-(1-naphthyloxy)-H-benzimidazole]; the metabolite will be referred to as alpha.SO. Changes resulting from drug treatment were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and tubulin immunocytochemistry (ICC). SEM revealed that disruption to the tegumental surface mainly took the form of swelling and blebbing. Extensive spine loss occurred on the ventral surface of the oral cone, and sloughing of the tegument was observed along the lateral margins of the fluke. Examination of sections from the anterior mid-body region at the TEM level revealed that treatment with alpha.SO led to swelling of the basal infolds and mitochondria within the tegumental syncytium; also, accumulations of secretory bodies beneath the apical plasma membrane. The tegumental cell bodies contained swollen mitochondria and cisternae of granular endoplasmic reticulum, but few Golgi complexes were observed. An increase in T2 secretory bodies was observed, whilst in the T1 tegumental cells, the T1 secretory bodies had decreased in number. Immunocytochemical (ICC) studies showed that incubation with alpha.SO, ABZ.SO and TCBZ.SO did not cause significant changes to the distribution of tubulin within the tegumental syncytium of the Sligo isolate. In contrast, alpha.SO, ABZ.SO and TCBZ.SO caused severe disruption to tubulin organization within the syncytial layer of the TCBZ-susceptible Cullompton isolate. The EM results confirm that compound alpha is a fasciolicide capable of disrupting the tegument of mature TCBZ-resistant F. hepatica; however, this was not accompanied by any change in tubulin immunoreactivity.
将耐三氯苯达唑的斯莱戈分离株的成熟肝片吸虫在体外与10微克/毫升的化合物α[5-氯-2-甲硫基-6-(1-萘氧基)-H-苯并咪唑]的亚砜代谢物一起孵育；该代谢物将被称为α.SO。通过扫描电子显微镜（SEM）、透射电子显微镜（TEM）和微管蛋白免疫细胞化学（ICC）检查药物处理引起的变化。SEM显示，体表表面的破坏主要表现为肿胀和起泡。口锥腹面出现广泛的棘突缺失，并且在吸虫的侧缘观察到体表脱落。在TEM水平检查中体前部区域的切片显示，用α.SO处理导致体表合胞体内的基底褶皱和线粒体肿胀；此外，顶端质膜下方有分泌小体聚集。体表细胞体含有肿胀的线粒体和颗粒内质网的池，但观察到的高尔基体复合物很少。观察到T2分泌小体增加，而在T1体表细胞中，T1分泌小体的数量减少。免疫细胞化学（ICC）研究表明，用α.SO、阿苯达唑亚砜（ABZ.SO）和三氯苯达唑亚砜（TCBZ.SO）孵育不会导致斯莱戈分离株体表合胞体内微管蛋白的分布发生显著变化。相比之下，α.SO、ABZ.SO和TCBZ.SO对三氯苯达唑敏感的卡勒姆普顿分离株合胞体层内的微管蛋白组织造成严重破坏。电子显微镜结果证实，化合物α是一种能够破坏成熟的耐三氯苯达唑肝片吸虫体表的杀吸虫剂；然而，这并未伴随着微管蛋白免疫反应性的任何变化。
