In Vitro Activity of Novel Metronidazole Derivatives on Larval Stages of Echinococcus Granulosus

Abstract

The effects of metronidazole (MTZ) and novel synthesized MTZ derivatives on in vitro cultured Echinococcus granulosus protoscoleces (PSCs), 30 day old segmentation stage and hydatid cysts (HC) developing secondarily in BALB/c mice were compared to those caused upon treatment with comparable doses of albandazole (ABZ) and mebendazole (MBZ) drugs. The highest protoscolicidal action resulted from the use of a non-schiff based MTZ derivative (MTZ-w: 4-[2-(2-methyl-5nitro-1H-imidazol-1-yl) ethyoxy] benzeyldehyde). Incubation of PSCs with MTZ-w concentrations of 25, 12.5 and 6.25 µg/ml resulted in significantly higher mortality rates than those caused by ABZ or MBZ at all periods post incubation. Total mortality of PSCs always occurred one day earlier using MTZ-w. Moreover, incubation of PSCs with MTZ-w at 6.25 µg/ml concentration resulted in greater mortality of PSCs than that caused by ABZ at 25ug/ml concentration. Three other MTZ derivatives showed similar in vitro effects on PSCs to those caused by ABZ or MTZ. Light microscopy revealed that changes in PSCs exposed to MTZ derivatives and ABZ reflected their relative actions in targeting scolex hooks, suckers and tegument. MTZ-w and ABZ caused rupture of hooks, deformation in suckers and disintegration in tegument of both PSCs and in vitro cultured segmentation stage. Less detrimental changes occurred upon the exposure to other MTZ derivatives. Exposure of HC to MTZ-w and ABZ caused regression in their size, damage in germinal membrane, fragmentation of underlining tissue, and scaling of laminated membrane. MTZ-w warrants further assessment as a potential chemotherapeutic drug against cystic echinococcosis in both animals and humans.