The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica.
OBJECTIVE
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 microg/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 microg/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.
Keiser
Jennifer
J
Swiss Tropical Institute, CH-4002 Basel, Switzerland. jennifer.keiser@unibas.ch
Utzinger
Jürg
J
Tanner
Marcel
M
Dong
Yuxiang
Y
Vennerstrom
Jonathan L
JL
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001652:Bile Ducts / Q000469:parasitology; D004195:Disease Models, Animal; D004449:Echinostoma / Q000187:drug effects* / Q000648:ultrastructure; D004451:Echinostomiasis / Q000188:drug therapy* / Q000469:parasitology; D005210:Fasciola hepatica / Q000187:drug effects*; D005211:Fascioliasis / Q000188:drug therapy* / Q000469:parasitology; D005260:Female; D051379:Mice; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar
D000980:Antiplatyhelmintic Agents; C518172:OZ78 compound; D000218:Adamantane