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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.

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The authors acknowledge the Brazilian Ministry of Education, and the Ministry of Science and Technology of Brazil for the scholarship provided to RO (CNPq BJT-A) through the program Science without Borders and São Paulo Research Foundation–FAPESP (RO: grant no. 2018/03108-0); DSM acknowledges CAPES for the PhD scholarship ‘Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001’. CKG is grateful to CNPq for the ‘Bolsas de Produtividade’; NFO and RCS acknowledge CNPq for the ‘Bolsa de Iniciação Científica’.


The present study received financial support from the Federal District Research Foundation (FAP-DF; edital da água—05/2016).

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Correspondence to Rhaul Oliveira.

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The experiments are in accordance with the current laws of the country in which they were performed. The study was approved by the ethics committee, at the University of Brasilia (reference no 100226/2014).

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de Oliveira, R.C.S., Oliveira, R., Rodrigues, M.A.C. et al. Lethal and Sub-lethal Effects of Nitrofurantoin on Zebrafish Early-Life Stages. Water Air Soil Pollut 231, 54 (2020).

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  • Antibiotics
  • Danio rerio embryos
  • Behaviour
  • Biochemical markers
  • Pharmaceuticals