Cytotoxicity induced by bismuth subcitrate in Giardia lamblia trophozoites

The cytotoxicity of colloidal bismuth subcitrate (CBS) was investigated in cultured Giardia lamblia trophozoites on the basis of cell attachment, morphology and viability studies. The effects on cell membrane integrity were evaluated by the permeability to trypan blue, and the morphological alterations were studied by phase-contrast microscopy and transmission electron microscopy. Our data show that although CBS induced loss of cellular viability (morphological and regrowth studies), the cell membrane permeability was not altered. The attachment of G. lamblia trophozoites to culture vials was rapidly disrupted by CBS. Ultrastructural observations revealed that this drug promoted modifications on the cell shape, displacement of nucleus and of cytoskeletal structures, pronounced cytoplasmic vacuolization, dorsal and ventral protuberance of cytoplasmic membrane and heavy deposition of electron-dense precipitates in adhesive disc, nuclear membrane and cytoplasmic components. In contrast, membranes and microtubules were apparently undamaged. Some of these results suggest that the cytotoxicity of CBS to G. lamblia cultures is the result of its binding to cytoskeletal components. As Far as we know, this work is the first demonstration that bismuth subcitrate could kill a human protozoan parasite suggesting its potential in the therapy of giardiasis. (C) 1999 Elsevier Science Ltd. All rights reserved.