Fasciola hepatica: tegumental alterations in adult flukes following in vitro and in vivo administration of artesunate and artemether.
The tegumental changes in adult Fasciola hepatica induced by artemether and artesunate were assessed utilizing scanning electron microscopy (SEM). F. hepatica were incubated with artemether and artesunate for 48h at a concentration of 10microg/ml in the absence or presence of haemin. For the latter experiment both, a triclabendazole-resistant and sensitive F. hepatica isolate were used. For the in vivo studies rats were treated with single 200mg/kg oral doses of artemether and artesunate and flukes recovered from the bile ducts after 24-96h. SEM analysis of the flukes incubated in the presence of the drugs without haemin showed only minor and localized damage of the tegument. In the presence of haemin extensive tegumental damage, including sloughing, blebbing and eruptions, particularly in the ventral and dorsal mid-body and tail region, was evident. No difference in the extent of damage could be observed between artemether and artesunate and between the triclabendazole-resistant and non-resistant flukes. After 24h in vivo disruption of the tegument was evident in the artemether-treated flukes, and the damage increased in severity 48-72h post-treatment. Sloughing, swelling and extensive furrowing of the tegument was observed in several flukes, in particular in the tail region and the ventral apical cone region. In the artesunate treatment, tegumental damage was evident after 72h, but seemed slightly less pronounced when compared to the artemether-treated specimens examined at the same time point. Concluding our experiments confirm that artemether and artesunate are potent fasciocidal drugs and the tegument of adult F. hepatica appears to be a target for the action of these drugs.
Keiser
Jennifer
J
Swiss Tropical Institute, P.O. Box, CH-4002 Basel, Switzerland. jennifer.keiser@unibas.ch
Morson
Gianni
G
D000284:Administration, Oral; D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000494:pharmacology*; D000077332:Artesunate; D005210:Fasciola hepatica / Q000187:drug effects* / Q000648:ultrastructure; D005211:Fascioliasis / Q000188:drug therapy* / Q000469:parasitology; D005260:Female; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D000980:Antiplatyhelmintic Agents; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; D000077549:Artemether