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

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

In: Journal of Antimicrobial Chemotherapy, 2006, vol. 58, no. 6, p. 1193-1197

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    Titre
    • The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica
    Auteur
    • Keiser, Jennifer. Swiss Tropical Institute, PO Box CH-4002 Basel, Switzerland
    • Utzinger, Jürg. Swiss Tropical Institute, PO Box CH-4002 Basel, Switzerland
    • Tanner, Marcel. Swiss Tropical Institute, PO Box CH-4002 Basel, Switzerland
    • Dong, Yuxiang. College of Pharmacy, University of Nebraska Medical Center Nebraska, NE 68198-6025, USA
    • Vennerstrom, Jonathan L.. College of Pharmacy, University of Nebraska Medical Center Nebraska, NE 68198-6025, USA
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Journal of Antimicrobial Chemotherapy, 2006, vol. 58, no. 6, p. 1193-1197. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:301297
    Summary
    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