JAC Advance Access originally published online on October 5, 2006
Journal of Antimicrobial Chemotherapy 2006 58(6):1193-1197; doi:10.1093/jac/dkl408
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The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica
1 Swiss Tropical Institute, PO Box CH-4002 Basel, Switzerland 2 College of Pharmacy, University of Nebraska Medical Center Nebraska, NE 68198-6025, USA
Received 14 July 2006; returned 27 August 2006; revised 1 September 2006; accepted 12 September 2006
*Corresponding author. Tel: +41-61-284-8218; Fax: +41-61-284-8105; E-mail: jennifer.keiser{at}unibas.ch
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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