PUBLICATION
Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos
- Authors
- Pohl, J., Golovko, O., Carlsson, G., Örn, S., Schmitz, M., Ahi, E.P.
- ID
- ZDB-PUB-210606-1
- Date
- 2021
- Source
- Chemosphere 276: 130282 (Journal)
- Registered Authors
- Keywords
- Adverse outcome pathway, Gene Co-Expression network analysis, Gene regulatory network analysis, Toxicity mechanisms
- MeSH Terms
-
- Animals
- Carbamazepine/toxicity
- Ozone*/toxicity
- Sewage
- Water Pollutants, Chemical*/toxicity
- Zebrafish/genetics
- PubMed
- 34088109 Full text @ Chemosphere
Citation
Pohl, J., Golovko, O., Carlsson, G., Örn, S., Schmitz, M., Ahi, E.P. (2021) Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos. Chemosphere. 276:130282.
Abstract
Sewage effluent ozonation can reduce concentrations of chemical pollutants including pharmaceutical residues. However, the formation of potentially toxic ozonation byproducts (OBPs) is a matter of concern. This study sought to elucidate toxicity mechanisms of ozonated carbamazepine (CBZ), an anti-epileptic drug frequently detected in sewage effluents and surface water, in zebrafish embryos (Danio rerio). Embryos were exposed to ozonated and non-ozonated CBZ from 3 h post-fertilization (hpf) until 144 hpf. Embryotoxicity endpoints (proportion of dead and malformed embryos) were assessed at 24, 48, and 144 hpf. Heart rate was recorded at 48 hpf. Exposure to ozonated CBZ gave rise to cardiovascular-related malformations and reduced heart rate. Moreover, embryo-larvae exposed to ozonated CBZ displayed a lack of swim bladder inflation. Hence, the expression patterns of CBZ target genes involved in cardiovascular and embryonal development were investigated through a stepwise gene co-expression analysis approach. Two co-expression networks and their upstream transcription regulators were identified, offering mechanistic explanations for the observed toxicity phenotypes. The study presents a novel application of gene co-expression analysis elucidating potential toxicity mechanisms of an ozonated pharmaceutical with environmental relevance. The resulting data was used to establish a putative adverse outcome pathway (AOP).
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping