PUBLICATION
Usefulness of zebrafish in evaluating drug-induced teratogenicity in cardiovascular system
- Authors
- Watanabe, R., Nakanishi, Y., Nijoukubo, D., Teraoka, H., Ogasawara, H., Mori, K.
- ID
- ZDB-PUB-180722-1
- Date
- 2019
- Source
- Drug and chemical toxicology 42(6): 649-656 (Journal)
- Registered Authors
- Teraoka, Hiroki
- Keywords
- O-ethylhydroxylamine hydrochloride, Zebrafish, cardiovascular malformation, rat, teratogenicity
- MeSH Terms
-
- Animals
- Cardiovascular Abnormalities/chemically induced*
- Cardiovascular System/drug effects
- Cardiovascular System/physiopathology
- Disease Models, Animal*
- Embryo, Nonmammalian
- Ethylamines/toxicity
- Female
- Green Fluorescent Proteins/genetics
- Male
- Rats
- Rats, Sprague-Dawley
- Species Specificity
- Teratogenesis/drug effects*
- Teratogens/toxicity*
- Zebrafish
- PubMed
- 30025483 Full text @ Drug Chem. Toxicol.
Citation
Watanabe, R., Nakanishi, Y., Nijoukubo, D., Teraoka, H., Ogasawara, H., Mori, K. (2019) Usefulness of zebrafish in evaluating drug-induced teratogenicity in cardiovascular system. Drug and chemical toxicology. 42(6):649-656.
Abstract
To confirm the usefulness of zebrafish for evaluating the teratogenic potential of drug candidates, the effect of O-ethylhydroxylamine hydrochloride (OHY), which induces mutagenesis by methylation, was evaluated in teratogenicity studies in rats and zebrafish. In the rat teratogenicity study, OHY-induced cardiovascular malformations such as increased abnormal vascular structures and ventricular septal defects. In the teratogenicity study using zebrafish-injected microspheres and green fluorescent protein-expressing Tg zebrafish (flk1:EGFP), OHY exposure was associated with the loss or malformation of the mandibular arch, opercular artery, and fourth branchial arch. These results suggested that OHY-induced external malformations in zebrafish eleutheroembryos adequately reflect OHY's teratogenicity in rat fetuses. Moreover, the zebrafish teratogenicity study incorporating vascular morphological examinations, including those of blood vessels in the heart, head and trunk, is an easy and reliable screening method to detect potential drug-induced teratogenicity and phenotypic characteristics.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping