Ultrastructural changes induced in the tegument and gut of Fasciola hepatica following in vivo and in vitro drug treatment with nitroxynil (Trodax).
Male Sprague-Dawley rats were dosed orally with nitroxynil at a concentration of 40 mg/kg, and adult Fasciola hepatica were recovered after 24, 48 and 72 h. Fine structural changes to the tegument and gut were monitored by transmission electron microscopy. Flukes were also incubated for 24 h in vitro in nitroxynil at a concentration of 100 microg/ml. Following treatment in vivo, there was an accumulation and accelerated release of secretory bodies at the apex of the tegumental syncytium. Some swelling of the mucopolysaccharide masses surrounding the basal infolds was evident after 48 and 72 h. There was an initial accumulation of T1 secretory bodies at the base of the syncytium, but this decreased at 72 h, coinciding with a decline in their production in the tegumental cells. The mitochondria were consistently swollen in the tegumental cells. At 72 h, large vacuolations were observed between the muscle layers and there was flooding around the underlying tissues. Some tegumental cells were seen to be degenerating and beginning to disintegrate. After 24 h treatment in vitro, the basal infolds were swollen and the crystalline structure of the spines was disrupted. Flooding of the internal tissues was evident and, in the tegumental cells, Golgi complexes and secretory bodies were absent. The mitochondria in the tegumental cells were swollen. In the gastrodermal cells, changes were evident at the earliest time period in vivo. The lamellae were disrupted, few secretory bodies were present, the mitochondria and cisternae of granular endoplasmic reticulum (ger) were swollen and there was an increased number of secretory bodies. These changes became progressively more severe with time. Similar changes were evident following treatment in vitro; vesiculation of the ger was also seen. The results indicate that oral uptake is the predominant route of entry of nitroxynil into the fluke.
McKinstry
B
B
Parasite Proteomics and Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL.
Brennan
G P
GP
Halferty
L
L
Forbes
A B
AB
Fairweather
I
I
D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005210:Fasciola hepatica / Q000187:drug effects* / Q000648:ultrastructure*; D005211:Fascioliasis / Q000188:drug therapy* / Q000469:parasitology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D009611:Nitroxinil / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D000980:Antiplatyhelmintic Agents; D009611:Nitroxinil