PUBLICATION
Danio rerio embryos on Prozac - Effects on the detoxification mechanism and embryo development
- Authors
- Cunha, V., Rodrigues, P., Santos, M.M., Moradas-Ferreira, P., Ferreira, M.
- ID
- ZDB-PUB-160816-24
- Date
- 2016
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 178: 182-189 (Journal)
- Registered Authors
- Ferreira, Miguel Godinho, Santos, Manuel
- Keywords
- ABC transporters, Antioxidant enzymes, Fluoxetine, Nuclear receptors, Phase I and II, Zebrafish embryos
- MeSH Terms
-
- ATP-Binding Cassette Transporters/genetics
- ATP-Binding Cassette Transporters/metabolism
- Animals
- Catalase/genetics
- Catalase/metabolism
- Down-Regulation/drug effects
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Embryonic Development/drug effects*
- Fluoxetine/toxicity*
- Humans
- Oxidative Stress/drug effects
- Real-Time Polymerase Chain Reaction
- Superoxide Dismutase/genetics
- Superoxide Dismutase/metabolism
- Water Pollutants, Chemical/toxicity*
- Xenobiotics/toxicity
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 27513977 Full text @ Aquat. Toxicol.
Citation
Cunha, V., Rodrigues, P., Santos, M.M., Moradas-Ferreira, P., Ferreira, M. (2016) Danio rerio embryos on Prozac - Effects on the detoxification mechanism and embryo development. Aquatic toxicology (Amsterdam, Netherlands). 178:182-189.
Abstract
In the past decade the presence of psychopharmaceuticals, including fluoxetine (FLU), in the aquatic environment has been associated with the increasing trend in human consumption of these substances. Aquatic organisms are usually exposed to chronic low doses and, therefore, risk assessments should evaluate the effects of these compounds in non-target organisms. Teleost fish possess an array of active defence mechanisms to cope with the deleterious effects of xenobiotics. These include ABC transporters, phase I and II of cellular detoxification and oxidative stress enzymes. Hence, the present study aimed at characterising the effect of FLU on embryo development of the model teleost zebrafish (Danio rerio) concomitantly with changes in the detoxification mechanisms during early developmental phases. Embryos were exposed to different concentrations of FLU (0.0015, 0.05, 0.1, 0.5 and 0.8μM) for 80hours post fertilization. Development was screened and the impact in the transcription of key genes, i.e., abcb4, abcc1, abcc2, abcg2, cyp1a, cyp3a65, gst, sod, cat, ahr, pxr, pparα, pparβ, pparγ, rxraa, rxrab, rxrbb, rxrga, rxrgb, raraa, rarab, rarga evaluated. In addition, accumulation assays were performed to measure the activity of ABC proteins and antioxidant enzymes (CAT and Cu/ZnSOD) after exposure to FLU. Embryo development was disrupted at the lowest FLU concentration tested (0.0015μM), which is in the range of concentrations found in WWTP effluents. Embryos exposed to higher concentrations of FLU decreased Cu/Zn SOD, and increased CAT (0.0015 and 0.5μM) enzymatic activity. Exposure to higher concentrations of FLU decreased the expression of most genes belonging to the detoxification system and upregulated cat at 0.0015μM of FLU. Most of the tested concentrations downregulated pparα, pparβ, pparγ, and raraa, rxraa, rxrab, rxrbb rxrgb and ahr gene expression while pxr was significantly up regulated at all tested concentrations. In conclusion, this study shows that FLU can impact zebrafish embryo development, at concentrations found in effluents of WWTPs, concomitantly with changes in antioxidant enzymes, and the transcription of key genes involved in detoxification and development. These finding raises additional concerns supporting the need to monitor the presence of this compound in aquatic reservoirs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping