PUBLICATION
Identification of proteome markers for drug-induced liver injury in zebrafish embryos
- Authors
- Driessen, M., Plas-Duivesteijn, S.V., Kienhuis, A.S., van den Brandhof, E.J., Roodbergen, M., van de Water, B., Spaink, H.P., Palmblad, M., van der Ven, L.T.M., Pennings, J.L.A.
- ID
- ZDB-PUB-220723-14
- Date
- 2022
- Source
- Toxicology 477: 153262 (Journal)
- Registered Authors
- Spaink, Herman P., van der Ven, Leo
- Keywords
- biomarker, drug-induced liver injury, hepatotoxicity, toxicoproteomics, zebrafish embryos
- MeSH Terms
-
- Animals
- Biomarkers/metabolism
- Chemical and Drug Induced Liver Injury*/etiology
- Chemical and Drug Induced Liver Injury*/metabolism
- Chromatography, Liquid
- Liver
- Proteome
- RNA-Binding Proteins/metabolism
- Tandem Mass Spectrometry
- Zebrafish*/physiology
- Zebrafish Proteins/genetics
- PubMed
- 35868597 Full text @ Toxicology
Citation
Driessen, M., Plas-Duivesteijn, S.V., Kienhuis, A.S., van den Brandhof, E.J., Roodbergen, M., van de Water, B., Spaink, H.P., Palmblad, M., van der Ven, L.T.M., Pennings, J.L.A. (2022) Identification of proteome markers for drug-induced liver injury in zebrafish embryos. Toxicology. 477:153262.
Abstract
The zebrafish embryo (ZFE) is a promising alternative non-rodent model in toxicology, and initial studies suggested its applicability in detecting hepatic responses related to drug-induced liver injury (DILI). Here, we hypothesize that detailed analysis of underlying mechanisms of hepatotoxicity in ZFE contributes to the improved identification of hepatotoxic properties of compounds and to the reduction of rodents used for hepatotoxicity assessment. ZFEs were exposed to nine reference hepatotoxicants, targeted at induction of steatosis, cholestasis, and necrosis, and effects compared with negative controls. Protein profiles of the individual compounds were generated using LC-MS/MS. We identified differentially expressed proteins and pathways, but as these showed considerable overlap, phenotype-specific responses could not be distinguished. This led us to identify a set of common hepatotoxicity marker proteins. At the pathway level, these were mainly associated with cellular adaptive stress-responses, whereas single proteins could be linked to common hepatotoxicity-associated processes. Applying several stringency criteria to our proteomics data as well as information from other data sources resulted in a set of potential robust protein markers, notably Igf2bp1, Cox5ba, Ahnak, Itih3b.2, Psma6b, Srsf3a, Ces2b, Ces2a, Tdo2b, and Anxa1c, for the detection of adverse responses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping