moxidectin and melarsonic-acid

The suitability of two viability parameters used for screening of antifilarial activities of new compounds was examined by parallel observation of the morphology. Male Onchocerca volvulus were exposed in vitro to 10 mumol mel w and milbemycin a and examined by light and transmission electron microscopy. The viability was assessed by measurement of the motility, using a micromotility meter and by determination of tetrazolium reduction. Already twelve hours after exposure to mel w the muscles of the body wall showed severe damage. After 36 hours the other tissues revealed degenerative changes and after 60 hours disintegration of all tissues was observed. Effects on the morphology caused by milbemycin a were seen earliest after 60 hours. Condensed cytoplasm in the hypodermal layer and beginning degeneration of spermatogenic stages indicated drug activity. The time-point of appearance of these drug induced morphological alterations was in accordance with the decrease of the motility indices and the degree of tetrazolium reduction. Morphological alterations indicating irreversible damage of worm tissues are a reliable parameter to detect macrofilaricidal activity. The good agreement between the results of the morphological examination and the assessment of the motility and the tetrazolium reduction confirms the suitability of the latter two assays for in vitro drug screening with O. volvulus.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Arsenicals; Filaricides; Ivermectin; Macrolides; Male; Microscopy, Electron; Movement; Onchocerca