Possible antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor, in mice model of Schistosoma–induced liver fibrosis

Abstract Liver fibrosis is a pathological process complicating schistosomiasis. It is an active process of continuous extracellular matrix accumulation. In Egypt, schistosomiasis re-infection is a continuing problem especially in rural areas. In this study we examined the antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor as a new molecular target for Schistosoma –induced liver fibrosis, in addition to exploring its effect as antischistosomal drug. The effect of GDC-0449 alone or combined with Praziquantel was tried experimentally in infected mice with Schistosoma mansoni . Fifty CD-1 Swiss female albino mice were used, forty mice were infected with Schistosoma mansoni cercariae. Animals were grouped into five groups; uninfected control, infected untreated, infected treated with Praziquantel (500 mg/kg/day) for two days, infected treated with GDC-0449 (40 mg/kg/day) for seven days, and infected treated with combined Praziquantel and GDC-0449. Parasitological and chemical parameters, hydroxyproline level and liver granuloma were assessed. Liver fibrosis was reduced significantly evidenced by reduced hydroxyproline levels [P