PUBLICATION

Ibuprofen and diclofenac impair the cardiovascular development of zebrafish (Danio rerio) at low concentrations

Authors
Zhang, K., Yuan, G., Werdich, A.A., Zhao, Y.
ID
ZDB-PUB-191217-2
Date
2019
Source
Environmental pollution (Barking, Essex : 1987)   258: 113613 (Journal)
Registered Authors
Keywords
Cardiac physiology, Diclofenac, Hemodynamics, Ibuprofen, Zebrafish
MeSH Terms
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal/administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal/toxicity*
  • Diclofenac/administration & dosage*
  • Diclofenac/toxicity*
  • Embryo, Nonmammalian/drug effects
  • Ibuprofen/administration & dosage*
  • Ibuprofen/toxicity*
  • Organogenesis/drug effects*
  • Water Pollutants, Chemical/adverse effects*
  • Zebrafish/embryology*
  • Zebrafish/growth & development*
PubMed
31838392 Full text @ Environ. Pollut.
Abstract
The non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen and diclofenac are highly prescribed worldwide and their presence in aquatic system may pose a potential risk to aquatic organisms. Here, we systematically assessed their cardiovascular disruptive effects in zebrafish (Danio rerio) at environmentally relevant concentrations between 0.04 and 25.0 μg/L. Ibuprofen significantly increased the cardiac outputs of zebrafish embryos at actual concentrations of 0.91, 4.3 and 21.9 μg/L. It up-regulated the blood cell velocity, total blood flow and down-regulated the blood cell density at concentrations of 4.3 μg/L and higher. In comparison, diclofenac led to inhibition of spontaneous muscle contractions and decreased hatching rate of zebrafish embryos at the highest concentration (24.1 μg/L), while it had negligible effects on the cardiac physiology and hemodynamics. Transcriptional analysis of biomarker genes involved in cardiovascular physiology, such as the significantly up-regulated nppa and nkx2.5 expressions response to ibuprofen but not to diclofenac, is consistent with these observations. In addition, both ibuprofen and diclofenac altered the morphology of intersegmental vessels at high concentrations. Our results revealed unexpected cardiovascular functional alterations of NSAIDs to fish at environmental or slightly higher than surface water concentrations and thus provided novel insights into the understanding of their potential environmental risks.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping