Effect of artemether, artesunate, OZ78, praziquantel, and tribendimidine alone or in combination chemotherapy on the tegument of Clonorchis sinensis. 2010

Jennifer Keiser, and Mireille Vargas
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. jennifer.keiser@unibas.ch

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.

UI MeSH Term Description Entries
D008855 Microscopy, Electron, Scanning Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY. Scanning Electron Microscopy,Electron Scanning Microscopy,Electron Microscopies, Scanning,Electron Microscopy, Scanning,Electron Scanning Microscopies,Microscopies, Electron Scanning,Microscopies, Scanning Electron,Microscopy, Electron Scanning,Microscopy, Scanning Electron,Scanning Electron Microscopies,Scanning Microscopies, Electron,Scanning Microscopy, Electron
D010655 Phenylenediamines Aniline compounds that contain two amino groups. They are used as a precursor in the synthesis of HETEROCYCLIC COMPOUNDS and POLYMERS. p-Phenylenediamine is used in the manufacture of HAIR DYES and is an ALLERGEN.
D011223 Praziquantel An anthelmintic used in most schistosome and many cestode infestations. Biltricide,Cesol,Cisticid,Cysticide,Droncit,Drontsit,EMBAY 8440,Prasiquantel,Praziquantel, (+-)-Isomer,Praziquantel, (R)-Isomer,Praziquantel, (S)-Isomer,Pyquiton,Traziquantel
D003003 Clonorchiasis Infection of the biliary passages with CLONORCHIS SINENSIS, also called Opisthorchis sinensis. It may lead to inflammation of the biliary tract, proliferation of biliary epithelium, progressive portal fibrosis, and sometimes bile duct carcinoma. Extension to the liver may lead to fatty changes and cirrhosis. (From Dorland, 27th ed) Clonorchis Infection,Clonorchis sinensis Infection,Opisthorchis sinensis Infection,Clonorchiases,Clonorchis Infections,Clonorchis sinensis Infections,Infection, Clonorchis,Infection, Clonorchis sinensis,Infection, Opisthorchis sinensis,Opisthorchis sinensis Infections
D003004 Clonorchis sinensis A species of trematode flukes of the family Opisthorchidae. Many authorities consider this genus belonging to Opisthorchis. It is common in China and other Asiatic countries. Snails and fish are the intermediate hosts. Opisthorchis sinensis,Clonorchis sinenses,Opisthorchis sinenses,sinenses, Opisthorchis,sinensis, Clonorchis
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005260 Female Females
D000077332 Artesunate A water-soluble, semi-synthetic derivative of the sesquiterpene lactone artemisinin with anti-malarial, anti-schistosomiasis, antiviral, and potential anti-neoplastic activities Dihydroartemisinine-12-alpha-succinate,Malacef,Malartin,SM 804,SM-804,Sodium Artesunate,Succinyl Dihydroartemisinin,Dihydroartemisinin, Succinyl,Dihydroartemisinine 12 alpha succinate,SM804
D000077549 Artemether An artemisinin derivative that is used in the treatment of MALARIA. Artemether, (3R-(3alpha,5abeta,6alpha,8abeta,9alpha,10beta,12beta,12aR*))-isomer,Artemether, (3R-(3alpha,5abeta,6beta,8aalpha,9alpha,10beta,12beta,12aR*))-isomer,Artemether, (3R-(3alpha,5abeta,6beta,8abeta,9alpha,10alpha,12beta,12aR*))-isomer,Artenam,O-Methyldihydroartemisinine,alpha-Artemether,beta-Arthemeter,O Methyldihydroartemisinine,alpha Artemether,beta Arthemeter
D000218 Adamantane A tricyclo bridged hydrocarbon. Diamantane

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