PUBLICATION
Prostaglandins prevent acetaminophen induced embryo toxicity in zebrafish (Danio rerio)
- Authors
- Galus, M., Fraz, S., Gugilla, A., Jönsson, M., Wilson, J.Y.
- ID
- ZDB-PUB-200822-27
- Date
- 2020
- Source
- Environmental Toxicology and Pharmacology 80: 103463 (Journal)
- Registered Authors
- Keywords
- Acetaminophen, Cyclooxygenase, Development, Gene expression, Prostaglandin
- MeSH Terms
-
- Acetaminophen/toxicity*
- Animals
- Dinoprostone/pharmacology*
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/enzymology
- Female
- Male
- Prostaglandin-Endoperoxide Synthases/genetics
- Zebrafish/abnormalities*
- Zebrafish/genetics
- PubMed
- 32822849 Full text @ Environ. Toxicol. Pharmacol.
Citation
Galus, M., Fraz, S., Gugilla, A., Jönsson, M., Wilson, J.Y. (2020) Prostaglandins prevent acetaminophen induced embryo toxicity in zebrafish (Danio rerio). Environmental Toxicology and Pharmacology. 80:103463.
Abstract
Previous research in our laboratory showed that acetaminophen (ACE) induced embryonic mortality and abnormalities in zebrafish. Here, we examined the dose response of ACE (0.05-50 μg L-1) in zebrafish embryos. Concentrations as low as 0.1 μg L-1 significantly increased abnormalities, and all test concentrations significantly increased mortality rates. In mammals, ACE inhibits cyclooxygenase (COX) enzymes to decrease prostaglandin production. Here we report COX activity and expression of the cox-1, cox-2a, and cox-2b genes in zebrafish embryos. COX activity was significantly inhibited by specific mammalian cox-1 (SC-560) and cox-2 (DuP-697) inhibitors in unexposed and ACE-exposed embryos. COX activity declined with development time. Maternal transcripts of all cox genes were found at 1 -h post fertilization and embryonic expression began in gastrulation or early segmentation. Co-exposure of ACE and prostaglandin E2 abolished the ACE-induced effects. This strongly supports that ACE elicits embryo toxicity in zebrafish though the same molecular mechanism of action of their therapeutic effects in mammals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping