PUBLICATION
Warfarin, a potential pollutant in aquatic environment acting through Pxr signaling pathway and γ-glutamyl carboxylation of vitamin K-dependent proteins
- Authors
- Fernández, I., Santos, A., Cancela, M.L., Laizé, V., Gavaia, P.J.
- ID
- ZDB-PUB-140806-2
- Date
- 2014
- Source
- Environmental pollution (Barking, Essex : 1987) 194C: 86-95 (Journal)
- Registered Authors
- Cancela, Leonor
- Keywords
- Pregnane X receptor, Skeletal deformities, Vitamin K, Warfarin, Zebrafish
- MeSH Terms
-
- Animals
- Protein Binding/drug effects
- Receptors, Steroid/metabolism
- Signal Transduction/drug effects
- Vitamin K/metabolism*
- Warfarin/toxicity*
- Water Pollutants, Chemical/toxicity*
- Zebrafish/metabolism
- PubMed
- 25094061 Full text @ Environ. Pollut.
- CTD
- 25094061
Citation
Fernández, I., Santos, A., Cancela, M.L., Laizé, V., Gavaia, P.J. (2014) Warfarin, a potential pollutant in aquatic environment acting through Pxr signaling pathway and γ-glutamyl carboxylation of vitamin K-dependent proteins. Environmental pollution (Barking, Essex : 1987). 194C:86-95.
Abstract
Warfarin-induced vitamin K (VK) recycling impairment is used worldwide as a rodenticide and human thromboembolic prophylactic. Since VK metabolism/signaling pathways have been conserved throughout vertebrate evolution, its release to the environment might impact on aquatic organisms. Present study assessed the toxic effect of warfarin (0, 5, 25 and 125 mg L(-1)) on zebrafish development and characterized underlying mechanisms of action through qPCR analysis of VK-related genes. Expression of pregnane X receptor (pxr), the nuclear receptor binding vitamin K, was ubiquitous in zebrafish and suggests that warfarin exposure may interfere with several biological processes. Indeed, warfarin exposure of zebrafish larvae caused hemorrhages in brain, skeletal deformities and triggered ectopic calcifications, which may be the consequence of an altered γ-carboxylation of VK-dependent proteins and/or pxr signaling. This study provides new insights into warfarin effects as a bone homeostasis disruptor and soft tissue calcification inductor, and its potential risk for aquatic environments.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping