PUBLICATION
Glucocorticoid mixtures of fluticasone propionate, triamcinolone acetonide and clobetasol propionate induce additive effects in zebrafish embryos
- Authors
- Willi, R.A., Salgueiro-González, N., Carcaiso, G., Fent, K.
- ID
- ZDB-PUB-190414-3
- Date
- 2019
- Source
- Journal of hazardous materials 374: 101-109 (Journal)
- Registered Authors
- Keywords
- Fluticasone propionate, Glucocorticoids, Mixtures, Triamcinolone acetonide, Zebrafish embryo
- MeSH Terms
-
- Animals
- Clobetasol/pharmacology*
- Drug Synergism
- Fluticasone/pharmacology*
- Gene Expression Profiling
- Gene Expression Regulation, Developmental
- Glucocorticoids/pharmacology*
- Heart Rate/drug effects
- Risk Assessment
- Triamcinolone Acetonide/pharmacology*
- Water Pollutants, Chemical/toxicity
- Zebrafish/embryology*
- PubMed
- 30981015 Full text @ J. Hazard. Mater.
Citation
Willi, R.A., Salgueiro-González, N., Carcaiso, G., Fent, K. (2019) Glucocorticoid mixtures of fluticasone propionate, triamcinolone acetonide and clobetasol propionate induce additive effects in zebrafish embryos. Journal of hazardous materials. 374:101-109.
Abstract
Many synthetic glucocorticoids from medical applications occur in the aquatic environment. Whether they pose a risk for fish health is poorly known. Here we investigate effects of glucocorticoids fluticasone propionate (FLU) and triamcinolone acetonide (TRI) as single steroids and as ternary mixtures with clobetasol propionate (CLO) in zebrafish embryos. Exposure to FLU and TRI in a range of concentrations between 0.099 and 120.08 μg/L led to concentration-related decrease in muscle contractions and increase in heart rate at 0.98 and 1.05 μg/L, respectively, and higher. Genes encoding for proteins related to glucose metabolism (g6pca, pepck1), immune system regulation (fkbp5, irg1l, socs3, gilz) and matrix metalloproteinases mmp-9 and mmp-13 showed expressional alterations, as well as genes encoding for the progestin receptor (pgr) and corticosteroid dehydrogenase (hsd11b2). FLU accelerated hatching and led to embryotoxicity (immobilization and edema). Ternary mixtures (FLU + TRI + CLO) induced the same physiological and toxicological effects at concentrations of individual glucocorticoids of 11.1-16.37 μg/L and higher. Heart rate was increased in the mixture at concentrations as low as 0.0885-0.11 μg/L of each steroid. Glucocorticoids in mixtures showed additive activity; the fold-changes of transcripts of 19 target genes were additive. Together, our data show that glucocorticoids act additively and their joint activity may be of concern for developing fish in contaminated environments.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping