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

Pohl, Johannes and Golovko, Oksana and Carlsson, Gunnar and Örn, Stefan and Schmitz, Monika and Ahi, Ehsan Pashay (2021). Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos. Chemosphere. 276 , 130282
[Research article]

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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). (C) 2021 The Author(s). Published by Elsevier Ltd.

Authors/Creators:Pohl, Johannes and Golovko, Oksana and Carlsson, Gunnar and Örn, Stefan and Schmitz, Monika and Ahi, Ehsan Pashay
Title:Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos
Series Name/Journal:Chemosphere
Year of publishing :2021
Volume:276
Article number:130282
Number of Pages:12
Publisher:PERGAMON-ELSEVIER SCIENCE LTD
ISSN:0045-6535
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 105 Earth and Related Environmental Sciences > Environmental Sciences (social aspects to be 507)
Keywords:Toxicity mechanisms, Gene Co-Expression network analysis, Gene regulatory network analysis, Adverse outcome pathway
URN:NBN:urn:nbn:se:slu:epsilon-p-112210
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-112210
Additional ID:
Type of IDID
DOI10.1016/j.chemosphere.2021.130282
Web of Science (WoS)000648339700126
ID Code:24500
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
(NL, NJ) > Dept. of Aquatic Sciences and Assessment
Deposited By: SLUpub Connector
Deposited On:10 Jun 2021 14:43
Metadata Last Modified:10 Jun 2021 14:51

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