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Updated: May 16, 2025
Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
Safety evaluation of microbisporicin (NAI-107) using zebrafish (Danio rerio) embryo-a pilot study
Zina Gestels1, Saïd Abdellati2, Andy Willaert3
1STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium.
Abstract:
NAI-107 has demonstrated in vitro and in vivo efficacy against multidrug-resistance (MDR) pathogens. Studies using the Galleria mellonella model found NAI-107 effective against Neisseria gonorrhoeae and vanB-resistant Enterococcus faecium, with no toxicity at concentrations up to 64 µg/ml. This pilot study evaluated NAI-107's safety using transgenic zebrafish embryos (kdrl:eGFP) that were exposed to NAI-107 concentrations of 0, 10, 20, and 30 µM from 5 hours post-fertilization (hpf) to 4 days post-fertilization (dpf). No mortality or significant morphological abnormalities were observed across all treatment groups. At 2 dpf, larvae treated with 20 and 30 µM NAI-107 exhibited a significant increase in heart rate (P < 0.05), although other cardiac parameters remain unaffected. At 4 dpf, larvae displayed no significant growth differences but had increased locomotor activity at 20 and 30 µM NAI-107 groups, indicated by the higher total distance moved and mean velocity (P < 0.05). NAI-107, at concentrations up to 30 µM, did not induce significant toxic effects in zebrafish embryos. The absence of adverse impacts on survival or gross morphology suggests a favorable safety margin. However, the observed increases in heart rate and locomotor activity suggest possible subclinical effects at higher concentrations that warrant further investigation.
Insights
NAI-107 shows promise against drug-resistant pathogens, with a pilot study in zebrafish embryos revealing no significant toxicity. However, higher concentrations did increase heart rate and locomotor activity, warranting further investigation.
Area of Science:
- Pharmacology and Toxicology
- Developmental Biology
- Antimicrobial Resistance
Background:
- NAI-107 exhibits in vitro and in vivo efficacy against multidrug-resistant (MDR) pathogens.
- Previous studies in Galleria mellonella models showed NAI-107 effectiveness against Neisseria gonorrhoeae and vanB-resistant Enterococcus faecium without toxicity.
Purpose of the Study:
- To evaluate the safety profile of NAI-107 in a transgenic zebrafish embryo model.
- To identify potential toxic effects or subclinical impacts of NAI-107 exposure during early development.
Main Methods:
- Transgenic zebrafish embryos (kdrl:eGFP) were exposed to NAI-107 at concentrations of 0, 10, 20, and 30 µM from 5 hours post-fertilization to 4 days post-fertilization.
- Assessed endpoints included mortality, morphological abnormalities, heart rate, cardiac parameters, growth, and locomotor activity.
Main Results:
- No mortality or significant morphological abnormalities were observed across all NAI-107 treatment groups.
- A significant increase in heart rate was noted at 2 days post-fertilization (dpf) for concentrations of 20 and 30 µM (P < 0.05).
- At 4 dpf, increased locomotor activity (total distance moved and mean velocity) was observed at 20 and 30 µM NAI-107 (P < 0.05), with no significant growth differences.
Conclusions:
- NAI-107 demonstrated a favorable safety margin in zebrafish embryos up to 30 µM, with no adverse effects on survival or gross morphology.
- Observed increases in heart rate and locomotor activity at higher concentrations suggest potential subclinical effects that require further investigation.
- The zebrafish embryo model provides a valuable platform for assessing the safety of novel antimicrobial agents like NAI-107.
