The effect of triclabendazole ("Fasinex") on protein synthesis by the liver fluke, Fasciola hepatica.
The effect of the active sulphoxide metabolite of the anthelmintic triclabendazole (TCBZ-SX, 15-50 micrograms ml-1) on the incorporation of radioactively labelled [14C] leucine by adult Fasciola hepatica tissue slices was measured by liquid scintillation counting. In addition, the ability of the microfilament-disrupting drug, cytochalasin B, and the microtubule-disrupting drug, tubulozole-C, to inhibit protein synthesis, was assessed by similar methods and compared with TCBZ-SX. The established protein synthesis inhibitors, cycloheximide and actinomycin D were used as positive controls. All the drugs showed a significant inhibition of protein synthesis, albeit to different extents; however, TCBZ-SX was the most potent, with no significant difference between its effect and that of cycloheximide or actinomycin D. Moreover, the concentration of TCBZ-SX, above 15 micrograms ml-1, had little further influence on incorporation of [14C] leucine. This investigation demonstrates the inhibitory effect of TCBZ-SX, cytochalasin B and tubulozole-C on protein synthesis in F. hepatica and confirms the qualitative observations made in several previous ultrastructural studies.
Stitt
A W
AW
School of Biology and Biochemistry, Queen's University of Belfast, Northern Ireland.
Fairweather
I
I
Mackender
R O
RO
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology; D004148:Dioxolanes / Q000494:pharmacology; D005210:Fasciola hepatica / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000493:pharmacokinetics; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077682:Triclabendazole
D001562:Benzimidazoles; D004148:Dioxolanes; D011500:Protein Synthesis Inhibitors; D003571:Cytochalasin B; D000077682:Triclabendazole; C040422:tubulazole; D007930:Leucine