PUBLICATION
Acute indomethacin exposure impairs cardiac development by affecting cardiac muscle contraction and inducing myocardial apoptosis in zebrafish (Danio rerio)
- Authors
- Liu, Y., Shi, X., Lu, C., Kou, G., Wu, X., Meng, X., Lv, Y., Luo, J., Cui, W., Yang, X.
- ID
- ZDB-PUB-240902-7
- Date
- 2024
- Source
- Ecotoxicology and environmental safety 283: 116976116976 (Journal)
- Registered Authors
- Liu, Yi, Lu, Chunjiao, Luo, Juanjuan, Yang, Xiaojun
- Keywords
- Cardiac development, Cardiac muscle contraction, Developmental toxicity, Indomethacin, Myocardial apoptosis, Zebrafish
- MeSH Terms
-
- Zebrafish*
- Cardiotoxicity
- Anti-Inflammatory Agents, Non-Steroidal*/toxicity
- Water Pollutants, Chemical/toxicity
- Heart*/drug effects
- Myocardial Contraction/drug effects
- Embryo, Nonmammalian*/drug effects
- Apoptosis*/drug effects
- Indomethacin*/toxicity
- Animals
- Myocardium/pathology
- PubMed
- 39216225 Full text @ Ecotoxicol. Environ. Saf.
Citation
Liu, Y., Shi, X., Lu, C., Kou, G., Wu, X., Meng, X., Lv, Y., Luo, J., Cui, W., Yang, X. (2024) Acute indomethacin exposure impairs cardiac development by affecting cardiac muscle contraction and inducing myocardial apoptosis in zebrafish (Danio rerio). Ecotoxicology and environmental safety. 283:116976116976.
Abstract
The accumulation of the active pharmaceutical chemical in the environment usually results in environmental pollution to increase the risk to human health. Indomethacin is a non-steroidal anti-inflammatory drug that potentially causes systemic and developmental toxicity in various tissues. However, there have been few studies for its potential effects on cardiac development. In this study, we systematically determined the cardiotoxicity of acute indomethacin exposure in zebrafish at different concentrations with morphological, histological, and molecular levels. Specifically, the malformation and dysfunction of cardiac development, including pericardial oedema, abnormal heart rate, the larger distance between the venous sinus and bulbus arteriosus (SV-BA), enlargement of the pericardial area, and aberrant motor capability, were determined after indomethacin exposure. In addition, further investigation indicated that indomethacin exposure results in myocardial apoptosis in a dose-dependent manner in zebrafish at early developmental stage. Mechanistically, our results revealed that indomethacin exposure mainly regulates key cardiac development-related genes, especially genes related to the cardiac muscle contraction-related signaling pathway, in zebrafish embryos. Thus, our findings suggested that acute indomethacin exposure might cause cardiotoxicity by disturbing the cardiac muscle contraction-related signaling pathway and inducing myocardial apoptosis in zebrafish embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping