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  4. Biotransformation Capacity of Zebrafish (Danio rerio) Early Life Stages: Functionality of the Mercapturic Acid Pathway
 
research article

Biotransformation Capacity of Zebrafish (Danio rerio) Early Life Stages: Functionality of the Mercapturic Acid Pathway

Tierbach, Alena  
•
Groh, Ksenia J.
•
Schonenberger, Rene
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August 1, 2020
Toxicological Sciences

Zebrafish (Danio rerio) early life stages offer a versatile model system to study the efficacy and safety of drugs or other chemicals with regard to human and environmental health. This is because, aside from the well-characterized genome of zebrafish and the availability of a broad range of experimental and computational research tools, they are exceptionally well suited for high-throughput approaches. Yet, one important pharmacokinetic aspect is thus far only poorly understood in zebrafish embryo and early larvae: their biotransformation capacity. Especially, biotransformation of electrophilic compounds is a critical pathway because they easily react with nucleophile molecules, such as DNA or proteins, potentially inducing adverse health effects. To combat such adverse effects, conjugation reactions with glutathione and further processing within the mercapturic acid pathway have evolved. We here explore the functionality of this pathway in zebrafish early life stages using a reference substrate (1-chloro-2,4-dinitrobenzene, CDNB). With this work, we show that zebrafish embryos can biotransform CDNB to the respective glutathione conjugate as early as 4h postfertilization. At all examined life stages, the glutathione conjugate is further biotransformed to the last metabolite of the mercapturic acid pathway, the mercapturate, which is slowly excreted. Being able to biotransform electrophiles within the mercapturic acid pathway shows that zebrafish early life stages possess the potential to process xenobiotic compounds through glutathione conjugation and the formation of mercapturates. The presence of this chemical biotransformation and clearance route in zebrafish early life stages supports the application of this model in toxicology and chemical hazard assessment.

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Type
research article
DOI
10.1093/toxsci/kfaa073
Web of Science ID

WOS:000593270200007

Author(s)
Tierbach, Alena  
Groh, Ksenia J.
Schonenberger, Rene
Schirmer, Kristin  
Suter, Marc J-F
Date Issued

2020-08-01

Publisher

OXFORD UNIV PRESS

Published in
Toxicological Sciences
Volume

176

Issue

2

Start page

355

End page

365

Subjects

Toxicology

•

biotransformation capacity

•

cdnb

•

gst

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high-resolution mass spectrometry

•

targeted proteomics

•

nontoxic concentration

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glutathione-s-transferase

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hepatic glutathione

•

perfused rat

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1-chloro-2,4-dinitrobenzene

•

metabolism

•

conjugate

•

expression

•

excretion

•

genes

•

disposition

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
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Available on Infoscience
December 13, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/174030
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