The metabolic profile of adult Fasciola hepatica obtained from rafoxanide-treated sheep.
Sheep infected with adult Fasciola hepatica were drenched with rafoxanide. At 4, 8, 16 and 24 h after drenching the sheep were killed and the flukes removed, washed and rapidly frozen in liquid nitrogen. The content of key metabolites in the fermentation pathway were determined and compared with those in control F. hepatica, whose hosts were not treated with rafoxanide. Rafoxanide decreased glycogen, malate, NADH and ATP levels. The level of other metabolites in the pathway increased for the first 8-16 h after rafoxanide treatment. The marked decrease in ATP and glycogen, and the increase in total [NAD+]/[NADH] and [oxaloacetate]/[malate], together with the changed content of other metabolites, led to the conclusion that the mode of action of rafoxanide against F. hepatica in vivo is by uncoupling oxidative phosphorylation.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005210:Fasciola hepatica / Q000378:metabolism*; D005211:Fascioliasis / Q000188:drug therapy / Q000662:veterinary*; D005285:Fermentation; D006003:Glycogen / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D011888:Rafoxanide / Q000627:therapeutic use*; D012457:Salicylamides / Q000627:therapeutic use*; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy*
D012457:Salicylamides; D009243:NAD; D011888:Rafoxanide; D000249:Adenosine Monophosphate; D009249:NADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006003:Glycogen