title: A transmission electron microscope study on the route of entry of triclabendazole into the liver fluke, Fasciola hepatica.
abstract: 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.
authors.affiliation: 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.
authors.forename: E
authors.initials: E
authors.lastname: Toner
authors.forename: G P
authors.initials: GP
authors.lastname: Brennan
authors.forename: F
authors.initials: F
authors.lastname: McConvery
authors.forename: M
authors.initials: M
authors.lastname: Meaney
authors.forename: I
authors.initials: I
authors.lastname: Fairweather
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics* / Q000494:pharmacology; D001562:Benzimidazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D005210:Fasciola hepatica / Q000378:metabolism*; D005211:Fascioliasis / Q000188:drug therapy* / Q000469:parasitology*; D008109:Liver Diseases, Parasitic / Q000188:drug therapy* / Q000469:parasitology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077682:Triclabendazole
chemical_list: D000871:Anthelmintics; D001562:Benzimidazoles; D000077682:Triclabendazole