Fasciola gigantica causes a worldwide waterborne/foodborne zoonotic disease in which humans
are incidental hosts. Fascioliasis has a major impact on human health and its control
mainly depends on triclabendazole (TCBZ). Unfortunately, the effectiveness of this drug is
decreased because of indiscriminate use resulting in development of resistance. Therefore, the
search for another effective anthelmintic is now compulsory. This work aimed to evaluate
the in vitro anthelmintic effects of auranofin (a thioredoxin reductase inhibitor) on adult F. gigantica
in comparison with the drug of choice; TCBZ. This study involved in vitro petri dish
incubation of seventy-five adult F. gigantica worms of nearly equal size with the tested drugs
and classified into five groups (fifteen worms each) as follows; G1 served as a control group,
subjected to motility and egg hatchability assays, histopathological and ultrastructural studies,
glutathione-S-transferase and superoxide dismutase assay, and cathepsin-L gene expression
analysis. Auranofin in all concentrations significantly decreased adult motility and egg hatchability.
It induced histopathological and ultrastructural deformities including apoptosis. Auranofin
in higher concentrations significantly suppressed the activity of the detoxifying enzyme;
glutathione-S-transferase, and significantly stimulated superoxide dismutase enzyme activity
reflecting the oxidative stress. At all concentrations, it suppressed the expression of the cathepsin-
L gene responsible for Fasciola invasive function.