In vitro and in vivo effects of 3-bromopyruvate against Echinococcus metacestodes

Abstract

AbstractWhile searching for novel anti-echinococcosis drugs, we have been focusing on glycolysis which is relied on byEchinococcusfor energy production and intermediates for other metabolic processes. The aim of this study was to investigate the potential therapeutic implication of glycolytic inhibitors onEchinococcus. Our results demonstrate that at an initial concentration of 40 μM, all inhibitors of glycolysis used in the current experiment [3-bromopyruvate (3-BrPA), ornidazole, clorsulon (CLS), sodium oxamate and 2,6-dihydroxynaphthalene (NA-P2)] show considerable in vitro effects againstEchinococcus granulosusprotoscoleces andEchinococcus multilocularismetacestodes. Among them, 3-BrPA exhibited the highest activity which was similar to that of nitazoxanide (NTZ) and more efficacious than albendazole (ABZ). The activity of 3-BrPA was dose dependent and resulted in severe ultrastructural destructions, as visualized by electron microscopy. An additional in vivo study in mice infected withE. multilocularismetacestodes indicates a reduction in parasite weight after the twice-weekly treatment of 25 mg/kg 3-BrPA for 6 weeks, compared to that of the untreated control. In particular, in contrast to ABZ, the administration of 25 mg/kg 3-BrPA did not cause toxicity to the liver and kidney in mice. Similarly, at the effective dose againstEchinococcuslarvae, 3-BrPA showed no significant toxicity to human hepatocytes. Taken together, the results suggest that interfering with the glycolysis of the parasite may be a novel chemotherapeutical option and 3-BrPA, which exhibited a remarkable activity againstEchinococcus, may be a promising potential drug against cystic echinococcosis (CE) and alveolar echinococcosis (AE).