Lethal and Sub-lethal Effects of Nitrofurantoin on Zebrafish Early-Life Stages

Antibiotics are among the most extensively used pharmaceuticals worldwide. They are natural or synthetic drugs with the capacity to kill or inhibit the growth of microorganisms. Several antibiotics have been detected in aquatic environments, but little is known about their effects on non-target organisms, especially fish. The aim of this study was to evaluate the effects of the antibiotic nitrofurantoin (NTF) using zebrafish embryos as model organisms. To assess mortality and development effects, the embryos were exposed to 0, 4, 9, 44, 100, 223 and 500 mg/L of NTF. A sub-lethal range of concentrations (0, 0.001, 0.02, 0.32, 5.62 and 100 mg/L) was used for biomarker analyses, namely cholinesterase, lactate dehydrogenase, glutathione S-transferase and catalase. The results indicated low toxicity of NTF to zebrafish, with a 168 h-LC50 value of 129.2 mg/L. The main effect on development was the loss of equilibrium related to the uninflated swim bladder (168 h-EC50 = 96.72 mg/L). Biomarker activity was induced in concentrations as low as 0.02 mg/L (cholinesterase, lactate dehydrogenase, glutathione S-transferase). Exposure to NTF induced no significant effects on zebrafish larvae behaviour. In summary, short-term exposure of zebrafish embryos to NTF induced developmental alterations only at high concentrations. However, biochemical changes occurred at lower levels of exposure, suggesting long-term effects on fish populations.