Esketamine induces embryonic and cardiac malformation through regulating the nkx2.5 and gata4 in zebrafish DOI Creative Commons
Shuang Li, Rui Zhao,

Tingyu Jiang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 7, 2024

Abstract Esketamine (EK) has been widely used in the treatment of depression, but effects EK prenatal on embryonic heart development have rarely reported. This study assesses varying concentrations and cardiogenesis to determine teratogenic concentration zebrafish model, centering interaction with genes nkx2.5 gata4 elucidate mechanism cardiac morphogenesis. Zebrafish embryos were classified into six distinct groups exposed either a vehicle or ascertain half lethal (LC50) at 48 hours post-fertilization (hpf) 72hpf through enumerating statistics mortality rates. Embryonic morphologies assessed utilizing live embryo imaging techniques stereo microscopy. Nkx2.5 identified via whole-mount situ hybridization. Exposure results concentration- time- dependent significant embryos. The 48h- 72h-LC50 for 0.31 (95% CI, 0.22, 0.38) mg·mL-1 0.17 CI，0.11, 0.24) mg·mL-1, respectively. A reduction rates body length observed distance between sinus venosus bulbar artery (SV-BA) was also found expanded, pericardial edema area showed swelling, axis curvature more pronounced exposure groups. WISH analysis staining intensity significantly decreased, while expression notably increased direct proportion increase. Our findings suggest that leads malformations, primarily due down-regulation over-expression gata4. insights advocate maintain equilibrium compensatory spatiotemporal regulation gene is paramount importance.

Language: Английский

Zebrafish as a Vertebrate Model for High-Throughput Drug Toxicity Screening: Mechanisms, Novel Techniques, and Future Perspectives DOI Creative Commons
W. Wang,

Xuan Gao,

Lin Liu

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101195 - 101195

Published: Jan. 1, 2025

Language: Английский

Citations

0
Esketamine induces embryonic and cardiac malformation through regulating the nkx2.5 and gata4 in zebrafish DOI Creative Commons
Shuang Li, Xiang Li, Rui Zhao

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 28, 2025

Esketamine (EK) has been widely used in the treatment of depression, but effects EK prenatal on embryonic heart development have rarely reported. This study assesses varying concentrations and cardiogenesis to determine teratogenic concentration zebrafish model, centering interaction between genes nkx2.5 gata4 elucidate mechanisms underlying cardiac morphogenesis. Zebrafish embryos were classified into six distinct groups exposed either a vehicle or ascertain median lethal (LC50) at 48 72 h post-fertilization (hpf) analyzing mortality rate data. Embryonic morphologies assessed utilizing live embryo imaging techniques stereo microscopy. Nkx2.5 identified via whole-mount situ hybridization (WISH) reverse transcription quantitative polymerase chain reaction (RT-qPCR). Exposure leads significant embryos, which are both concentration- time-dependent. The h- h-LC50 for 1.30 (95% CI 0.92, 1.60) millimolar (mM) 0.71 0.46, 1.01) mM, respectively. A reduction rates body length observed distance sinus venosus bulbar artery (SV-BA) was found expanded, pericardial edema area showed swelling, axis curvature more pronounced exposure groups. Both WISH an RT-qPCR analysis staining intensity expression significantly decreased, while assay results opposite direction. Our findings indicate that malformations, primarily due down-regulation over-expression gata4. Equilibrium maintenance compensatory crucial spatiotemporal gene regulation.

Language: Английский

Citations

0
New Psychoactive Substance Esketamine Causes Endocrine-Disrupting Effects and Developmental Toxicity DOI
Siying Li,

Dongdong Ma,

Wenjun Shi

et al.

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

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 certain environmental concentration remains unclear. In this study, zebrafish embryos and ZF4 cells were exposed (0, 0.12, 1.02, 10.6 μg L-1, marked by SC, LC, MC, HC, respectively) 14 days post fertilization (dpf) 24 h, respectively. Biphasic dose responses induced observed after h exposure. ESK-LC ESK-MC obviously increased embryo area length, height, volume yolk sac, whereas ESK-HC had the opposite effect. appreciably upregulated transcription expression levels vtg, disrupting cell cycle After dpf exposure, KEGG analysis indicated that circadian rhythm, nucleotide excision repair, estrogen signaling pathways top three impacted pathways, with significantly enhancing gene these except cyp7a1 bh1he41. Correspondingly, notably VTG level, aligning relatively high affinity receptors, as analyzed through molecular docking. Our research demonstrated exhibits developmental endocrine-disrupting effects zebrafish, highlighting need address ecological fish.

Language: Английский

Citations

0
Esketamine Exposure Impairs Cardiac Development and Function in Zebrafish Larvae DOI Creative Commons
Shuo Huang, Jingyi Wang, Tingting Lin

et al.

Toxics, Journal Year: 2024, Volume and Issue: 12(6), P. 427 - 427

Published: June 13, 2024

Esketamine is a widely used intravenous general anesthetic. However, its safety, particularly effects on the heart, not fully understood. In this study, we investigated of esketamine exposure zebrafish embryonic heart development. Zebrafish embryos were exposed to at concentrations 1, 10, and 100 mg/L from 48 h post-fertilization (hpf) 72 hpf. We found that after exposure, had an increased hatching rate, decreased stroke volume, cardiac output. When transgenic Tg(

Language: Английский

Citations

2
Ecotoxicological Risk Assessment of the Novel Psychoactive Substance Esketamine: Emphasis on Fish Skeletal, Behavioral, and Vascular Development DOI
Qiong Zhang,

Tianjie Wu,

Congying Luo

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 480, P. 135823 - 135823

Published: Sept. 11, 2024

Language: Английский

Citations

2
Multi-omics reveal toxicity mechanisms underpinning nanoplastic in redclaw crayfish (Cherax quadricarinatus) DOI
Tian Zhu, Chunxia Yao,

Shuang Hong

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 951, P. 175680 - 175680

Published: Aug. 22, 2024

Language: Английский

Citations

1
Esketamine induces embryonic and cardiac malformation through regulating the nkx2.5 and gata4 in zebrafish DOI Creative Commons
Shuang Li, Rui Zhao,

Tingyu Jiang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 7, 2024

Abstract Esketamine (EK) has been widely used in the treatment of depression, but effects EK prenatal on embryonic heart development have rarely reported. This study assesses varying concentrations and cardiogenesis to determine teratogenic concentration zebrafish model, centering interaction with genes nkx2.5 gata4 elucidate mechanism cardiac morphogenesis. Zebrafish embryos were classified into six distinct groups exposed either a vehicle or ascertain half lethal (LC50) at 48 hours post-fertilization (hpf) 72hpf through enumerating statistics mortality rates. Embryonic morphologies assessed utilizing live embryo imaging techniques stereo microscopy. Nkx2.5 identified via whole-mount situ hybridization. Exposure results concentration- time- dependent significant embryos. The 48h- 72h-LC50 for 0.31 (95% CI, 0.22, 0.38) mg·mL-1 0.17 CI，0.11, 0.24) mg·mL-1, respectively. A reduction rates body length observed distance between sinus venosus bulbar artery (SV-BA) was also found expanded, pericardial edema area showed swelling, axis curvature more pronounced exposure groups. WISH analysis staining intensity significantly decreased, while expression notably increased direct proportion increase. Our findings suggest that leads malformations, primarily due down-regulation over-expression gata4. insights advocate maintain equilibrium compensatory spatiotemporal regulation gene is paramount importance.

Language: Английский

Citations

0