1. Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos
- Author
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Monika Schmitz, Stefan Örn, Johannes Pohl, Ehsan Pashay Ahi, Gunnar E. Carlsson, Oksana Golovko, and Organismal and Evolutionary Biology Research Programme
- Subjects
ADVERSE OUTCOME PATHWAYS ,Health, Toxicology and Mutagenesis ,0208 environmental biotechnology ,PROTEIN ,02 engineering and technology ,010501 environmental sciences ,Pharmacology ,01 natural sciences ,Adverse Outcome Pathway ,Zebrafish ,biology ,Sewage ,Chemistry ,1184 Genetics, developmental biology, physiology ,Environmental Sciences (social aspects to be 507) ,Embryo ,General Medicine ,Miljövetenskap ,Pollution ,3. Good health ,FAMILY ,Carbamazepine ,Toxicity ,embryonic structures ,HEART ,Toxicity mechanisms ,medicine.drug ,OZONATION ,PHARMACEUTICAL RESIDUES ,EXPRESSION ,Environmental Engineering ,animal structures ,Danio ,Adverse outcome pathway ,Ozone ,medicine ,Environmental Chemistry ,Animals ,Gene Co-Expression network analysis ,Swim bladder inflation ,0105 earth and related environmental sciences ,Public Health, Environmental and Occupational Health ,RELATIVE QUANTIFICATION ,General Chemistry ,Gene regulatory network analysis ,biology.organism_classification ,FRAMEWORK ,020801 environmental engineering ,MODEL ,Gene co-expression network ,Environmental Sciences ,Water Pollutants, Chemical - 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.
- Published
- 2020