Teratogenic evaluation of metronidazole and ornidazole using Drosophila melanogaster as an experimental model.
BACKGROUND
Drosophila and vertebrates show similarities that suggest that the mechanisms involved in the induction of developmental defects may be similar in both. Therefore, Drosophila has been proposed as a useful, rapid, and economical model in the preliminary screening for teratology studies. The objective of the present study was to investigate the effect of metronidazole (MTZ) and ornidazole (ONZ) on the developmental stages of Drosophila melanogaster.


METHODS
Samarkand wild-type females were allowed to lay eggs for 24 hr in media containing MTZ or ONZ at concentrations of 0, 500, 1000, and 2000 microg/ml. When larvae completed their development, the emerging flies were counted and examined for morphological abnormalities.


RESULTS
After the analysis of 400-1000 flies for each concentration, ONZ-treated flies did not show an incidence of malformations above control values, although a significant high number of individuals with reduced body size was observed (p < 0.005, chi2 test). On the other hand, the 1000- and 2000-microg/ml MTZ-treated series presented higher frequencies of total abnormalities than did concurrent and historic controls (p < 0.05, chi2 test), indicating an MTZ effect during developmental morphogenesis.


CONCLUSIONS
These findings contribute to the characterization of both nitroimidazoles, which are widely used, especially in underdeveloped countries. At the same time, this Drosophila bioassay is sensitive enough to detect differential effects of MTZ and ONZ (abnormalities vs. growth effects), showing specificity and selectivity.
Palermo
Ana María
AM
CITEFA (Instituto Investigaciones Científicas y Técnicas de las FFAA), Buenos Aires, Argentina. apalermo@citefa.gov.ar
Reynoso
A S
AS
López Nigro
M
M
Carballo
M A
MA
Mudry
M D
MD
D000005:Abdomen / Q000002:abnormalities; D000014:Abnormalities, Drug-Induced; D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects*; D004331:Drosophila melanogaster / Q000187:drug effects*; D007814:Larva / Q000187:drug effects; D008795:Metronidazole / Q000009:adverse effects*; D009950:Ornidazole / Q000009:adverse effects*; D013909:Thorax / Q000002:abnormalities / Q000187:drug effects
D000981:Antiprotozoal Agents; D008795:Metronidazole; D009950:Ornidazole