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JAC Advance Access published online on October 5, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl408
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received July 14, 2006
Revised September 1, 2006
Accepted September 12, 2006

Original article

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

Jennifer Keiser 1 *, Jürg Utzinger 1, Marcel Tanner 1, Yuxiang Dong 2, and Jonathan L. Vennerstrom 2

1 Swiss Tropical Institute, PO Box, CH-4002 Basel, Switzerland
2 College of Pharmacy, University of Nebraska Medical Center, Nebraska, NE 68198-6025, USA

* To whom correspondence should be addressed.
Jennifer Keiser, E-mail: jennifer.keiser{at}unibas.ch


  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.

Keywords: food-borne trematodiasis; 1,2,4-trioxolanes; in vivo studies; in vitro studies; scanning electron microscopy.
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