Parasite Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland.
Parasitology. 2010 Apr;137(5):855-70. doi: 10.1017/S0031182009991247. Epub 2009 Dec 24.
Uptake of triclabendazole by the liver fluke, Fasciola hepatica has been studied by experiments designed to block either oral uptake of drug, by use of ligatures, or trans-tegumental diffusion, by allowing the drug to bind to an excess of bovine serum albumin (BSA) in the medium. Changes to the tegumental system, musculature and gut were assessed using transmission electron microscopy. Flukes were incubated in vitro for 24 h in TCBZ.SO (15 microg/ml). Disruption to the tegument and muscle was similar in ligatured and non-ligatured flukes, suggesting that closing the oral route did not affect drug uptake. The ultrastructure of the gastrodermal cells remained unchanged. Non-ligatured flukes were also incubated for 24 h in vitro in TCBZ.SO (15 microg/ml) in the presence of red blood cells (RBCs). Oral uptake of blood was demonstrated, but gut ultrastructure remained normal, whereas the tegument was severely disrupted. In separate experiments, ligatured and non-ligatured flukes were incubated in TCBZ.SO (15 microg/ml) in the presence of BSA (30 mg/ml) for 24 h in vitro. There was a marked decrease in the degree of tegumental disruption observed compared with TCBZ.SO action alone; again, the gut remained normal. The findings support previous morphological and pharmacological studies indicating that trans-tegumental uptake of triclabendazole predominates in the liver fluke.
肝片形吸虫对三氯苯达唑的摄取已通过实验进行了研究,这些实验旨在通过使用结扎物阻断药物的口服摄取,或者通过允许药物与介质中过量的牛血清白蛋白(BSA)结合来阻止药物的跨体扩散。使用透射电子显微镜评估了体被系统、肌肉和肠道的变化。将吸虫在 TCBZ.SO(15μg/ml)中体外孵育 24 小时。结扎和未结扎的吸虫的体被和肌肉破坏相似,这表明关闭口服途径不会影响药物摄取。胃皮层细胞的超微结构保持不变。未结扎的吸虫也在体外以 TCBZ.SO(15μg/ml)和红细胞(RBC)存在的情况下孵育 24 小时。已经证明了血液的口服摄取,但肠道超微结构保持正常,而体被则严重受损。在单独的实验中,结扎和未结扎的吸虫在 TCBZ.SO(15μg/ml)和 BSA(30mg/ml)存在下孵育 24 小时。与 TCBZ.SO 单独作用相比,观察到的体被破坏程度明显降低;肠道仍然正常。这些发现支持先前的形态学和药理学研究,表明肝片形吸虫的三氯苯达唑主要通过体扩散摄取。