IN VITRO EVALUATION OF THIOREDOXIN REDUCTASE INHIBITOR (AURANOFIN) ACTIVITY IN COMPARISON WITH TRICLABENDAZOLE ON ADULT FASCIOLA GIGANTICA

Fasciola gigantica causes a worldwide waterborne/foodborne zoonotic disease in which humansare incidental hosts. Fascioliasis has a major impact on human health and its controlmainly depends on triclabendazole (TCBZ). Unfortunately, the effectiveness of this drug isdecreased because of indiscriminate use resulting in development of resistance. Therefore, thesearch for another effective anthelmintic is now compulsory. This work aimed to evaluatethe in vitro anthelmintic effects of auranofin (a thioredoxin reductase inhibitor) on adult F. giganticain comparison with the drug of choice; TCBZ. This study involved in vitro petri dishincubation of seventy-five adult F. gigantica worms of nearly equal size with the tested drugsand 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 expressionanalysis. Auranofin in all concentrations significantly decreased adult motility and egg hatchability.It induced histopathological and ultrastructural deformities including apoptosis. Auranofinin higher concentrations significantly suppressed the activity of the detoxifying enzyme;glutathione-S-transferase, and significantly stimulated superoxide dismutase enzyme activityreflecting the oxidative stress. At all concentrations, it suppressed the expression of the cathepsin-L gene responsible for Fasciola invasive function.