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Updated: May 23, 2025
Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
Embryotoxicity Evaluation of Novel Synthetic Cannabinoid 4F-MDMB-BUTICA Using Zebrafish Embryos
Berşan Kullebi1, Ömercan Alat2, Özkan Aksakal3
1Department of Molecular Biology and Genetics, Science Faculty, Atatürk University, Erzurum, Türkiye.
Abstract:
Detailed studies on the embryotoxic and teratogenic effects of synthetic cannabinoids known to be abused are very limited. The present study aimed to evalutate the possible embryotoxic, teratogenic, behavioral, and molecular effects of 4F-MDMB-BUTICA, a new generation synthetic cannabinoid, using zebrafish embryos. The zebrafish embryos were exposed to the cannabinoid at 0.15, 0.30, 0.60, 1.20, 2.40, and 4.80 mg/L from 3 to 24 hpf (acute) and 3 to 120 hpf (subacute). No developmental abnormalities and mortality were observed in embryos after acute exposure. Subacute 4F-MDMB-BUTICA exposure induced mortality of the embryos with the 120 hpf LC50 and EC50 of 1.932 and 0.960 mg/L, respectively. 4F-MDMB-BUTICA also caused embryonic deformities, including spine formation, pericardial edema, impaired blood flow, yolk sac edema, and delayed development. Additionally, subacute cannabinoid exposure induced hypoactivity in response to the stimulus in 120-hpf larvae. qPCR analyses were performed on a subset of 19 genes associated with specific adverse outcomes. The cannabinoid exposure altered the transcriptional expression levels of apoptosis (casp3a, casp8, ifng1, and tp53) DNA repair (rad51), dopamine (dat, drd1, and drd3), serotonin (5ht1aa, 5ht1a, 5ht1b, and 5ht2c), γ-aminobutyric acid (gabra1, gat1, abat, and gad1b), and behavior (gnrh3, gnrhr3, and kiss2)-related genes. In conclusion, the subacute exposure to 4F-MDMB-BUTICA induces mortality, developmental toxicity, hypoactivity of larval behavior, and changes in some essential genes in zebrafish. These findings suggest that 4F-MDMB-BUTICA may have similar embryotoxic effects in humans.
Insights
New synthetic cannabinoid 4F-MDMB-BUTICA causes mortality and developmental defects in zebrafish embryos after subacute exposure. This study reveals significant behavioral and molecular changes, suggesting potential human health risks.
Area of Science:
- Developmental toxicology
- Neuropharmacology
- Molecular biology
Background:
- Limited data exists on the embryotoxic and teratogenic effects of abused synthetic cannabinoids.
- New generation synthetic cannabinoids like 4F-MDMB-BUTICA require urgent toxicological evaluation.
Purpose of the Study:
- To evaluate the embryotoxic, teratogenic, behavioral, and molecular effects of 4F-MDMB-BUTICA in zebrafish embryos.
- To determine the acute and subacute toxicity of 4F-MDMB-BUTICA.
Main Methods:
- Zebrafish embryos were exposed to 4F-MDMB-BUTICA at various concentrations (0.15–4.80 mg/L) during acute (3–24 hpf) and subacute (3–120 hpf) periods.
- Developmental abnormalities, mortality, and larval behavior were assessed.
- Quantitative PCR (qPCR) was used to analyze gene expression related to apoptosis, DNA repair, neurotransmission, and behavior.
Main Results:
- Acute exposure showed no adverse effects.
- Subacute exposure resulted in significant mortality (LC50 = 1.932 mg/L, EC50 = 0.960 mg/L) and developmental deformities (spine, pericardial edema, yolk sac edema, delayed development).
- Larvae exhibited hypoactivity, and qPCR revealed altered expression of genes involved in apoptosis, DNA repair, dopamine, serotonin, GABAergic systems, and behavior.
Conclusions:
- Subacute exposure to 4F-MDMB-BUTICA induces mortality, developmental toxicity, and behavioral changes in zebrafish.
- The observed molecular alterations suggest potential mechanisms for toxicity.
- Findings indicate that 4F-MDMB-BUTICA may pose similar embryotoxic risks to humans.
