New Psychoactive Substance Esketamine Causes Endocrine-Disrupting Effects and Developmental Toxicity.
Si-Ying Li, Dongdong Ma, Wen-Jun Shi, Jin-Ge Zhang, Bo Tang, Zhi-Jie Lu, Chong-Rui Yao, Xiao-Bing Long, Xin Liu, Chu-Shu Huang, Guang-Guo Ying
Environmental science & technology May 6, 2025 DOI: 10.1021/acs.est.5c00589 via PubMed
Summary
AI-generated from the abstractEsketamine (ESK), a hallucinogenic new psychoactive substance found in surface waters worldwide, causes developmental toxicity and endocrine disruption in zebrafish. Zebrafish embryos exposed to low and medium concentrations (0.12 and 1.02 μg/L) showed increased embryo area, yolk sac size, and upregulated vitellogenin (vtg) gene expression, while the highest concentration (10.6 μg/L) produced opposite effects. After 14 days, ESK altered circadian rhythm, DNA repair, and estrogen signaling pathways, and elevated vitellogenin protein levels, consistent with its binding affinity for estrogen receptors. These findings indicate that environmentally relevant ESK concentrations pose ecological risks to fish.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Zebrafish embryos and ZF4 cells |
| Intervention | Esketamine |
| Dose | 0, 0.12, 1.02, and 10.6 μg L-1 |
| Duration | 14 days post-fertilization for embryos; 24 hours for ZF4 cells |
| Topics | Esketamine |
| Keywords | Developmental toxicity Endocrine-disrupting effects New psychoactive substance Zebrafish |
| Citations | 3 |
| Key finding | Esketamine at environmental concentrations induces biphasic developmental effects and endocrine disruption in zebrafish, including altered growth, yolk sac changes, and estrogenic activity. |
Abstract
Esketamine (ESK), a new psychoactive substance known for its strong hallucinogenic effect, has been detected in surface water worldwide. The toxicity of ESK to fish at a certain environmental concentration remains unclear. In this study, zebrafish embryos and ZF4 cells were exposed to ESK (0, 0.12, 1.02, and 10.6 μg L-1, marked by SC, LC, MC, and HC, respectively) for 14 days post fertilization (dpf) and 24 h, respectively. Biphasic dose responses induced by ESK were observed after 24 h of exposure. ESK-LC and ESK-MC obviously increased embryo area and length, height, and volume of yolk sac, whereas ESK-HC had the opposite effect. ESK-LC and ESK-MC appreciably upregulated the transcription and expression levels of vtg, disrupting the cell cycle after 24 h of exposure. After 14 dpf exposure, KEGG analysis indicated that circadian rhythm, nucleotide excision repair, and estrogen signaling pathways were the top three impacted pathways, with ESK significantly enhancing gene transcription in these three pathways, except for cyp7a1 and bh1he41. Correspondingly, ESK notably increased the VTG level, aligning with the relatively high affinity of estrogen receptors, as analyzed through molecular docking. Our research demonstrated that ESK exhibits developmental toxicity and endocrine-disrupting effects in zebrafish, highlighting the need to address its ecological toxicity in fish.