The cytotoxic effects of ciprofloxacin in Giardia lamblia trophozoites.
The cytotoxicity of ciprofloxacin was investigated in culture of Giardia lamblia (ATCC 30957), used as an in vitro cellular model, on the basis of cell growth, morphology, viability, adherence and metabolic studies. The effects on cell membrane integrity were evaluated by permeability of the cells to trypan blue, and the morphological alterations were studied by optical and transmission electronic microscopy. The metabolic studies were performed by measured oxygen uptake with a Clark-type oxygen electrode. Our data show that ciprofloxacin induces loss of viability with morphological alterations and loss of membrane integrity. Ultrastructural observations revealed that this drug promoted modifications on the cell shape, pronounced dorsal vesiculation, plasma membrane blebbing, disaggregation of ribosome, coagulation of cytoplasmic matrix, and heavy deposit of electron-dense precipitates on the cytoplasm and nucleus. Ciprofloxacin also inhibits parasite growth, adherence and O(2) uptake in a concentration-dependent manner. Some of these observations suggest that cytotoxicity of ciprofloxacin results in cell death by a necrosis process. We demonstrate that ciprofloxacin has a lethal effect in G. lamblia trophozoites and could be used as an alternative drug in giardiasis treatment, particularly in infections that are resistant to other antibiotics.
Sousa
M C
MC
Laboratory of Microbiology and Parasitology, University of Coimbra, 3030 Coimbra, Portugal. mcsousa@ci.uc.pt
Poiares-da-Silva
J
J
D000826:Animal Testing Alternatives; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002939:Ciprofloxacin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D016829:Giardia lamblia / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D066298:In Vitro Techniques; D008018:Life Cycle Stages / Q000187:drug effects* / Q000502:physiology; D008839:Microelectrodes; D008854:Microscopy, Electron; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D014343:Trypan Blue / Q000378:metabolism
D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D014343:Trypan Blue