title: A scanning electron microscope study on the route of entry of clorsulon into the liver fluke, Fasciola hepatica.
abstract: Three experiments were carried out in vitro to determine the roles of the tegument and gut of Fasciola hepatica in the uptake of the flukicidal drug, clorsulon. Changes to the two surfaces were assessed by scanning electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in clorsulon (10 microg/ml). The gastrodermal surface remained normal and few changes to the tegumental surface were observed. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. The gastrodermal surface was severely disrupted and the gut lamellae were disorganised and necrotic. Swelling of the tegument and blebbing on the tegumental surface were evident, but the changes were not severe. More severe swelling of the tegument was observed in the third experiment, in which flukes were incubated for 24 h in clorsulon (10 microg/ml), with both absorptive surfaces being available for drug uptake. The gastrodermal surface was badly disrupted and the gut lamellae were disorganised and necrotic. Taking the results of the three experiments together, the gastrodermal surface was more affected than the tegument and the greatest disruption to the two surfaces was seen when both routes of entry were available to the fluke. The data support a previous study which indicated that entry of clorsulon into the fluke in vivo is principally by the oral ingestion of drug bound to the red blood cells.
authors.affiliation: Parasite Proteomics and Therapeutics Research Group, School of Biology and Biochemistry, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, BT9 7BL, Belfast , Northern Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Meaney
authors.forename: S
authors.initials: S
authors.lastname: Haughey
authors.forename: G P
authors.initials: GP
authors.lastname: Brennan
authors.forename: I
authors.initials: I
authors.lastname: Fairweather
mesh_terms: D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D004064:Digestive System / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005210:Fasciola hepatica / Q000378:metabolism* / Q000472:pathogenicity / Q000648:ultrastructure*; D066298:In Vitro Techniques; D008026:Ligation; D008099:Liver / Q000469:parasitology; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D013424:Sulfanilamides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000980:Antiplatyhelmintic Agents; D013424:Sulfanilamides; C015675:clorsulon