Effect of artemether, artesunate, OZ78, praziquantel, and tribendimidine alone or in combination chemotherapy on the tegument of Clonorchis sinensis

Parasitol Int. 2010 Sep;59(3):472-6. doi: 10.1016/j.parint.2010.04.003. Epub 2010 Apr 20.

Abstract

We investigated the morphological effects of half-strength treatments with praziquantel, artemether, artesunate, OZ78 and tribendimidine as well as combinations of praziquantel with artemether, artesunate, OZ78 and tribendimidine and an artesunate-tribendimidine combination in rats harboring adult Clonorchis sinensis. Rats were infected with C. sinensis, dosed orally with single agents or combination treatments and flukes recovered at 3 or 5 days post-treatment. The number of flukes was counted, the viability recorded and surface changes monitored by scanning electron microscopy. Drug effects induced by the individual drugs at sub-curative doses 3 days post-treatment were minor with the exception of flukes recovered from rats treated with artemether and tribendimidine. Treatment with the praziquantel combinations of artesunate, OZ78 and tribendimidine did not produce a greater disruption of the tegument than the individual drugs 3 days post-treatment. On the other hand, at this time point many worms treated with artemether-praziquantel had died and eruptions, roughening or blebbing were observed on all worms examined. Five days post-treatment flukes exposed to any of the praziquantel combinations in rats had died. Rats treated with an artesunate-tribendimidine combination resulted in a rapid death of flukes, 3 days post-treatment all worms had been expelled. In conclusion, we have confirmed the promising clonorchicidal properties of different drug combinations in rats. Differences in the extent and time-scale of tegumental disruption have been observed. The effect of drug combinations against C. sinensis requires further scientific inquiry, e.g. in transmission electron microscopy studies and in the C. sinensis-rabbit model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Animals
  • Anthelmintics / therapeutic use*
  • Artemether
  • Artemisinins / therapeutic use*
  • Artesunate
  • Clonorchiasis / drug therapy*
  • Clonorchiasis / parasitology
  • Clonorchis sinensis / drug effects*
  • Clonorchis sinensis / ultrastructure
  • Drug Therapy, Combination
  • Female
  • Microscopy, Electron, Scanning
  • Phenylenediamines / therapeutic use*
  • Praziquantel / therapeutic use*
  • Rats
  • Rats, Wistar
  • Skin / drug effects
  • Skin / ultrastructure
  • Treatment Outcome

Substances

  • Anthelmintics
  • Artemisinins
  • OZ78 compound
  • Phenylenediamines
  • tribendimidine
  • Artesunate
  • Praziquantel
  • Artemether
  • Adamantane