Embryotoxicity of flumequine on Danio rerio: mortality, morphological/histological alterations and changes in calmoduline gene expression

Toxic and teratogenic effects of sub-acute exposure to 5 and 50 µg/l Flumequine (9-fluoro-6,7-dihydro-5-methyl-1-oxo-1H, 5H-benzene), an antibiotic used in aquaculture, have been investigated on Danio rerio. This model was chosen being easy to handle and particularly sensitive to chemical and physical stress during reproductive processes. Results showed that 35 days treatment (at both concentrations) cause a significant increase in embryos mortality rate, mainly due to a dramatic toxic effect in the first four days treatment. Furthermore 35 days treatment (at both concentrations) induced developmental alterations in trunk and unpaired fins: in particular, trunk is often thinner on both dorso-ventral and medium lateral axes, and developmental defects in cartilage, muscular and neural structures can be found. Muscular tissue was altered in the tail region: myosepta were irregular or absent; muscle bundles were discontiguous. In treated embryos a significant reduction of signal intensity in both trunk and dorsal branches of metameric spinal nerves was found by in situ hybridisation with a probe for calmoduline messenger RNA. These results account for the possible multiple effects on non target species of antimicrobial drug environmental contamination.