Teratogenic evaluation of metronidazole and ornidazole using Drosophila melanogaster as an experimental model

• Published in: Birth defects research. A Clinical and molecular teratology 2004-04, Vol.70 (4), p.157-162
• Main Authors: Palermo, Ana María, Reynoso, A.S., López Nigro, M., Carballo, M.A., Mudry, M.D.
• Format: Article
• Language: English
• Subjects: Abdomen - abnormalities; Abnormalities, Drug-Induced; Animals; Antiprotozoal Agents - adverse effects; Biological and medical sciences; Drosophila melanogaster; Drosophila melanogaster - drug effects; Drug toxicity and drugs side effects treatment; Larva - drug effects; Medical sciences; Metronidazole - adverse effects; Miscellaneous (drug allergy, mutagens, teratogens...); Ornidazole - adverse effects; Pharmacology. Drug treatments; Thorax - abnormalities; Thorax - drug effects
• ISSN: 1542-0752; 1542-0760
• DOI: 10.1002/bdra.20008

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 μg/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, χ2 test). On the other hand, the 1000‐ and 2000‐μg/ml MTZ‐treated series presented higher frequencies of total abnormalities than did concurrent and historic controls (p < 0.05, χ2 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. Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.