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

AbstractWhile searching for novel anti-echinococcosis drugs, we have been focusing on glycolysis which is relied on byEchinococcus for 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 granulosus protoscoleces andEchinococcus multilocularis metacestodes. 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. multilocularis metacestodes 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 againstEchinococcus larvae, 3-BrPA showed no significant toxicity to human hepatocytes. Taken together, the results suggest that interfering wi...
Source: Veterinary Research - Category: Veterinary Research Source Type: research