title: Fasciola hepatica: tegumental surface alterations following treatment in vivo and in vitro with nitroxynil (Trodax).
abstract: Male Sprague-Dawley rats were dosed orally with nitroxynil at a concentration of 40 mg/kg and adult Fasciola hepatica recovered after 24 h, 48 h and 72 h. Surface changes to the flukes were monitored by means of SEM. After the 24 h treatment, extensive swelling and blebbing of the tegument was observed on both surfaces, although the dorsal anterior region was more severely affected than either the posterior dorsal region or entire ventral surface. At high magnification, microvillus-like projections were evident, giving the surface a roughened appearance. After 48 h, the changes evident at 24 h had become more severe and some tegumental loss had occurred in the oral region of the fluke. Surface disruption was particularly evident along the lateral margins of the fluke in this region. In some specimens a single large swelling was present in the dorsal midbody region. The swelling was a more typical feature of flukes recovered. After 72 h, tegumental loss was more widespread, occurring over the oral cone and anterior midbody on the dorsal surface. Overall the dorsal surface was consistently more severely affected than the ventral surface, and the anterior region of the fluke was more disrupted than the posterior region. After 24 h in vitro incubation, the oral cone and midbody exhibited considerable spine loss and swelling. Overall, the dorsal surface was more disrupted than the ventral surface and the anterior region of the fluke was more disrupted than the posterior region. Regional differences in the response of the fluke to nitroxynil will be compared to previously published data with other fasciolicides. The results indicate that the tegument is an important target for nitroxynil action. Disruption of this, the fluke's main line of defence, would allow the drug access to other internal tissues, leading to more widespread damage.
authors.affiliation: Parasite Proteomics and Therapeutics Research Group, School of Biology and Biochemistry, The Queen's University of Belfast, BT97BL Belfast, Northern Ireland.
authors.forename: B
authors.initials: B
authors.lastname: McKinstry
authors.forename: I
authors.initials: I
authors.lastname: Fairweather
authors.forename: G P
authors.initials: GP
authors.lastname: Brennan
authors.forename: A B
authors.initials: AB
authors.lastname: Forbes
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D004817:Epidermis / Q000187:drug effects* / Q000469:parasitology; D005210:Fasciola hepatica / Q000187:drug effects* / Q000254:growth & development; D005211:Fascioliasis / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009611:Nitroxinil / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000871:Anthelmintics; D009611:Nitroxinil