Morphological response of triclabendazole-susceptible and triclabendazole-resistant isolates of Fasciola hepatica to treatment in vitro with nitroxynil (Trodax).
Adult liver flukes belonging to three isolates of differing sensitivity to triclabendazole were incubated for 24 h in vitro in nitroxynil at a concentration of 100 microg/ml. Fine structural changes to the tegument, sub-tegumental region and gut were assessed by transmission electron microscopy. Similar changes were observed in all three isolates. In the tegumental syncytium, the basal infoldings and mitochondria were swollen, and there was an accumulation and accelerated release of secretory bodies at the apex. The crystalline core of the spines was disrupted, and the tegumental covering sloughed off. Mitochondria in the tegumental cells were also swollen, the Golgi complexes were affected and reduced numbers of T1 secretory bodies were evident in the T1-type of tegumental cell. In the sub-tegumental region, large spaces were present between cells and tissues, indicative of severe internal flooding. Swelling of mitochondria and cisternae of the granular endoplasmic reticulum was seen in the gastrodermal cells, which contained few secretory bodies. The extent of disruption varied between the isolates: the triclabendazole-resistant Sligo isolate was the most severely affected, while the Fairhurst triclabendazole-susceptible isolate was the least affected. In all three isolates, the tegument was more severely affected than the gut.
McKinstry
B
B
Parasite Proteomics and Therapeutics Research Group, School of Biological Sciences, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9.7BL, Ireland, UK.
Halferty
L
L
Brennan
G P
GP
Fairweather
I
I
D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D004338:Drug Combinations; D004351:Drug Resistance; D005210:Fasciola hepatica / Q000187:drug effects* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009596:Nitrophenols / Q000494:pharmacology*; D009611:Nitroxinil / Q000494:pharmacology; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D013012:Sorbitol / Q000494:pharmacology*; D000077682:Triclabendazole
D000980:Antiplatyhelmintic Agents; D001562:Benzimidazoles; D004338:Drug Combinations; D009596:Nitrophenols; C023620:Trodax; D000077682:Triclabendazole; D013012:Sorbitol; D009611:Nitroxinil