A single dose of the antineoplastics hydroxyurea or cisplatin has praziquantel-like effects on Schistosoma mansoni worms and host mouse liver

Abstract

Increasing resistance to praziquantel, the only available antischistosomal drug, is always developed by schistosomes. The recent description of stem cell-like neoblasts in schistosomes led to the idea of applying antineoplastic drugs as antischistosomal agents that may inhibit stem cell divisions and retard worm regeneration. Here, we explored the in vitro and in vivo effect of some antineoplastic drugs on S. mansoni worm and the host mouse liver. S. mansoni worms' viability was tested after exposure to either praziquantel or one of the antitumor drugs (hydroxyurea, cisplatin, methotrexate, and colchicine) in vitro for 24 and 48 h. The effect of two of them (hydroxyurea and cisplatin) on worm burden, tegument ultrastructure, and host liver structure and function was tested in vivo in S. mansoni-infected mouse model. All drugs affected variably the worm burden in vitro. Hydroxyurea and cisplatin, like praziquantel, damaged the worm tegument, reduced worm burden, and viable schistosome eggs, decreased anti-schistosome IgG, reduced egg-induced hepatic granuloma size and cellularity, restored liver organization and improved liver function as represented by serum alanine aminotransferase and albumin. In conclusions, a single dose of hydroxyurea and cisplatin had anti-schistosome effects and may offer a safe promising alternative to control of schistosomiasis. A direct link between antitumor drugs and inhibition of schistosome neoblasts remains to be proven.