The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica

Jennifer Keiser, Jürg Utzinger, Marcel Tanner, Yuxiang Dong, Jonathan L. Vennerstrom

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Objectives: The trematocidal properties of a synthetic peroxide, 1,2,4-trioxolane (OZ78) were determined both in vivo and in vitro. Methods: Two weeks post-infection Echinostoma caproni-infected mice were administered single oral doses of 400-1000 mg/kg OZ78. Fasciola hepatica-infected rats were treated orally with 50-400 mg/kg OZ78 3 and 8-9 weeks post-infection. Worm burden reductions were assessed against untreated control animals. Adult F. hepatica were observed by scanning electron microscopy (SEM) after recovery from the bile duct of a rat 3 days after administration of a single oral dose of 100 mg/kg OZ78 and after in vitro exposure to concentrations of 1, 10 and 100 μg/mL OZ78. Results: In the E. caproni-mouse model 100% worm burden reductions were achieved with a single oral dose of 1000 mg/kg OZ78. A single dose of 100 mg/kg OZ78 resulted in worm burden reductions of 100% against juvenile and adult F. hepatica. F. hepatica recovered from rats 3 days post-treatment displayed feeble activity and some flukes had died. Typical features revealed by SEM included extensive blebbing and sloughing. Exposure of F. hepatica to 10-100 μg/mL OZ78 in vitro resulted in the death of all trematodes. F. hepatica showed focal blebbing and sloughing of the tegument at all concentrations investigated. Conclusions: Our data indicate that OZ78 is highly efficacious against F. hepatica and E. caproni and provide a sound platform for identification of a synthetic peroxide drug development candidate against major trematode infections.

Original languageEnglish (US)
Pages (from-to)1193-1197
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume58
Issue number6
DOIs
StatePublished - Dec 2006

Keywords

  • 1,2,4-trioxolanes
  • Food-borne trematodiasis
  • In vivo studies
  • Scanning electron microscopy

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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