Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos

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http://hdl.handle.net/10138/330300

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Pohl , J , Golovko , O , Carlsson , G , Örn , S , Schmitz , M & Pashay Ahi , E 2021 , ' Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos ' , Chemosphere , vol. 276 , 130282 . https://doi.org/10.1016/j.chemosphere.2021.130282

Title: Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos
Author: Pohl, Johannes; Golovko, Oksana; Carlsson, Gunnar; Örn, Stefan; Schmitz, Monika; Pashay Ahi, Ehsan
Other contributor: University of Helsinki, Organismal and Evolutionary Biology Research Programme
Date: 2021-08
Language: eng
Number of pages: 12
Belongs to series: Chemosphere
ISSN: 0045-6535
DOI: https://doi.org/10.1016/j.chemosphere.2021.130282
URI: http://hdl.handle.net/10138/330300
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).
Subject: 1184 Genetics, developmental biology, physiology
Toxicity mechanisms
Gene Co-Expression network analysis
Gene regulatory network analysis
Adverse outcome pathway
ADVERSE OUTCOME PATHWAYS
PHARMACEUTICAL RESIDUES
RELATIVE QUANTIFICATION
EXPRESSION
FRAMEWORK
OZONATION
PROTEIN
FAMILY
HEART
MODEL
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